Author: "Scheffer, IE" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Scheffer, IE"' showing total 914 results

Start Over Author "Scheffer, IE"

914 results on '"Scheffer, IE"'

251. PRRT2 Mutations Cause Benign Familial Infantile Epilepsy and Infantile Convulsions with Choreoathetosis Syndrome

Author: Heron, SE, Grinton, BE, Kivity, S, Afawi, Z, Zuberi, SM, Hughes, JN, Pridmore, C, Hodgson, BL, Iona, X, Sadleir, LG, Pelekanos, J, Herlenius, E, Goldberg-Stern, H, Bassan, H, Haan, E, Korczyn, AD, Gardner, AE, Corbett, MA, Gecz, J, Thomas, PQ, Mulley, JC, Berkovic, SF, Scheffer, IE, Dibbens, LM, Heron, SE, Grinton, BE, Kivity, S, Afawi, Z, Zuberi, SM, Hughes, JN, Pridmore, C, Hodgson, BL, Iona, X, Sadleir, LG, Pelekanos, J, Herlenius, E, Goldberg-Stern, H, Bassan, H, Haan, E, Korczyn, AD, Gardner, AE, Corbett, MA, Gecz, J, Thomas, PQ, Mulley, JC, Berkovic, SF, Scheffer, IE, and Dibbens, LM
Abstract: Benign familial infantile epilepsy (BFIE) is a self-limited seizure disorder that occurs in infancy and has autosomal-dominant inheritance. We have identified heterozygous mutations in PRRT2, which encodes proline-rich transmembrane protein 2, in 14 of 17 families (82%) affected by BFIE, indicating that PRRT2 mutations are the most frequent cause of this disorder. We also report PRRT2 mutations in five of six (83%) families affected by infantile convulsions and choreoathetosis (ICCA) syndrome, a familial syndrome in which infantile seizures and an adolescent-onset movement disorder, paroxysmal kinesigenic choreoathetosis (PKC), co-occur. These findings show that mutations in PRRT2 cause both epilepsy and a movement disorder. Furthermore, PRRT2 mutations elicit pleiotropy in terms of both age of expression (infancy versus later childhood) and anatomical substrate (cortex versus basal ganglia).
Published: 2012

252. Genome-wide association analysis of genetic generalized epilepsies implicates susceptibility loci at 1q43, 2p16.1, 2q22.3 and 17q21.32

Author: Steffens, M, Leu, C, Ruppert, A-K, Zara, F, Striano, P, Robbiano, A, Capovilla, G, Tinuper, P, Gambardella, A, Bianchi, A, La Neve, A, Crichiutti, G, de Kovel, CGF, Trenite, DK-N, de Haan, G-J, Lindhout, D, Gaus, V, Schmitz, B, Janz, D, Weber, YG, Becker, F, Lerche, H, Steinhoff, BJ, Kleefuss-Lie, AA, Kunz, WS, Surges, R, Elger, CE, Muhle, H, von Spiczak, S, Ostertag, P, Helbig, I, Stephani, U, Moller, RS, Hjalgrim, H, Dibbens, LM, Bellows, S, Oliver, K, Mullen, S, Scheffer, IE, Berkovic, SF, Everett, KV, Gardiner, MR, Marini, C, Guerrini, R, Lehesjoki, A-E, Siren, A, Guipponi, M, Malafosse, A, Thomas, P, Nabbout, R, Baulac, S, Leguern, E, Guerrero, R, Serratosa, JM, Reif, PS, Rosenow, F, Moerzinger, M, Feucht, M, Zimprich, F, Kapser, C, Schankin, CJ, Suls, A, Smets, K, De Jonghe, P, Jordanova, A, Caglayan, H, Yapici, Z, Yalcin, DA, Baykan, B, Bebek, N, Ozbek, U, Gieger, C, Wichmann, H-E, Balschun, T, Ellinghaus, D, Franke, A, Meesters, C, Becker, T, Wienker, TF, Hempelmann, A, Schulz, H, Rueschendorf, F, Leber, M, Pauck, SM, Trucks, H, Toliat, MR, Nuernberg, P, Avanzini, G, Koeleman, BPC, Sander, T, Steffens, M, Leu, C, Ruppert, A-K, Zara, F, Striano, P, Robbiano, A, Capovilla, G, Tinuper, P, Gambardella, A, Bianchi, A, La Neve, A, Crichiutti, G, de Kovel, CGF, Trenite, DK-N, de Haan, G-J, Lindhout, D, Gaus, V, Schmitz, B, Janz, D, Weber, YG, Becker, F, Lerche, H, Steinhoff, BJ, Kleefuss-Lie, AA, Kunz, WS, Surges, R, Elger, CE, Muhle, H, von Spiczak, S, Ostertag, P, Helbig, I, Stephani, U, Moller, RS, Hjalgrim, H, Dibbens, LM, Bellows, S, Oliver, K, Mullen, S, Scheffer, IE, Berkovic, SF, Everett, KV, Gardiner, MR, Marini, C, Guerrini, R, Lehesjoki, A-E, Siren, A, Guipponi, M, Malafosse, A, Thomas, P, Nabbout, R, Baulac, S, Leguern, E, Guerrero, R, Serratosa, JM, Reif, PS, Rosenow, F, Moerzinger, M, Feucht, M, Zimprich, F, Kapser, C, Schankin, CJ, Suls, A, Smets, K, De Jonghe, P, Jordanova, A, Caglayan, H, Yapici, Z, Yalcin, DA, Baykan, B, Bebek, N, Ozbek, U, Gieger, C, Wichmann, H-E, Balschun, T, Ellinghaus, D, Franke, A, Meesters, C, Becker, T, Wienker, TF, Hempelmann, A, Schulz, H, Rueschendorf, F, Leber, M, Pauck, SM, Trucks, H, Toliat, MR, Nuernberg, P, Avanzini, G, Koeleman, BPC, and Sander, T
Abstract: Genetic generalized epilepsies (GGEs) have a lifetime prevalence of 0.3% and account for 20-30% of all epilepsies. Despite their high heritability of 80%, the genetic factors predisposing to GGEs remain elusive. To identify susceptibility variants shared across common GGE syndromes, we carried out a two-stage genome-wide association study (GWAS) including 3020 patients with GGEs and 3954 controls of European ancestry. To dissect out syndrome-related variants, we also explored two distinct GGE subgroups comprising 1434 patients with genetic absence epilepsies (GAEs) and 1134 patients with juvenile myoclonic epilepsy (JME). Joint Stage-1 and 2 analyses revealed genome-wide significant associations for GGEs at 2p16.1 (rs13026414, P(meta) = 2.5 × 10(-9), OR[T] = 0.81) and 17q21.32 (rs72823592, P(meta) = 9.3 × 10(-9), OR[A] = 0.77). The search for syndrome-related susceptibility alleles identified significant associations for GAEs at 2q22.3 (rs10496964, P(meta) = 9.1 × 10(-9), OR[T] = 0.68) and at 1q43 for JME (rs12059546, P(meta) = 4.1 × 10(-8), OR[G] = 1.42). Suggestive evidence for an association with GGEs was found in the region 2q24.3 (rs11890028, P(meta) = 4.0 × 10(-6)) nearby the SCN1A gene, which is currently the gene with the largest number of known epilepsy-related mutations. The associated regions harbor high-ranking candidate genes: CHRM3 at 1q43, VRK2 at 2p16.1, ZEB2 at 2q22.3, SCN1A at 2q24.3 and PNPO at 17q21.32. Further replication efforts are necessary to elucidate whether these positional candidate genes contribute to the heritability of the common GGE syndromes.
Published: 2012

253. Familial focal epilepsy with variable foci mapped to chromosome 22q12: Expansion of the phenotypic spectrum

Author: Klein, KM, O'Brien, TJ, Praveen, K, Heron, SE, Mulley, JC, Foote, S, Berkovic, SF, Scheffer, IE, Klein, KM, O'Brien, TJ, Praveen, K, Heron, SE, Mulley, JC, Foote, S, Berkovic, SF, and Scheffer, IE
Abstract: We aimed to refine the phenotypic spectrum and map the causative gene in two families with familial focal epilepsy with variable foci (FFEVF). A new five-generation Australian FFEVF family (A) underwent electroclinical phenotyping, and the original four-generation Australian FFEVF family (B) (Ann Neurol, 44, 1998, 890) was re-analyzed, including new affected individuals. Mapping studies examined segregation at the chromosome 22q12 FFEVF region. In family B, the original whole genome microsatellite data was reviewed. Five subjects in family A and 10 in family B had FFEVF with predominantly awake attacks and active EEG studies with a different phenotypic picture from other families. In family B, reanalysis excluded the tentative 2q locus reported. Both families mapped to chromosome 22q12. Our results confirm chromosome 22q12 as the solitary locus for FFEVF. Both families show a subtly different phenotype to other published families extending the clinical spectrum of FFEVF.
Published: 2012

254. In vivo loss of slow potassium channel activity in individuals with benign familial neonatal epilepsy in remission

Author: Tomlinson, SE, Bostock, H, Grinton, B, Hanna, MG, Kullmann, DM, Kiernan, MC, Scheffer, IE, Berkovic, SF, Burke, D, Tomlinson, SE, Bostock, H, Grinton, B, Hanna, MG, Kullmann, DM, Kiernan, MC, Scheffer, IE, Berkovic, SF, and Burke, D
Abstract: Benign familial neonatal epilepsy is a neuronal channelopathy most commonly caused by mutations in KCNQ2, which encodes the K(v)7.2 subunit of the slow K(+) channel. K(v)7.2 is expressed in both central and peripheral nervous systems. Seizures occur in the neonatal period, often in clusters within the first few days of life, and usually remit by 12 months of age. The mechanism of involvement of K(v)7.2 mutations in the process of seizure generation has not been established in vivo. In peripheral axons, K(v)7.2 contributes to the nodal slow K(+) current. The present study aimed to determine whether axonal excitability studies could detect changes in peripheral nerve function related to dysfunction or loss of slow potassium channel activity. Nerve excitability studies were performed on eight adults with KCNQ2 mutations and a history of benign familial neonatal epilepsy, now in remission. Studies detected distinctive changes in peripheral nerve, indicating a reduction in slow K(+) current. Specifically, accommodation to long-lasting depolarizing currents was reduced in mutation carriers by 24% compared with normal controls, and the threshold undershoot after 100 ms depolarizing currents was reduced by 22%. Additional changes in excitability included a reduction in the relative refractory period, an increase in superexcitability and a tendency towards reduced sub-excitability. Modelling of the nerve excitability changes suggested that peripheral nerve hyperexcitability may have been ameliorated by upregulation of other potassium channels. We conclude that subclinical dysfunction of K(v)7.2 in peripheral axons can be reliably detected non-invasively in adulthood. Related alterations in neuronal excitability may contribute to epilepsy associated with KCNQ2 mutations.
Published: 2012

255. PRRT2 phenotypic spectrum includes sporadic and fever-related infantile seizures

Author: Scheffer, IE, Grinton, BE, Heron, SE, Kivity, S, Afawi, Z, Iona, X, Goldberg-Stern, H, Kinali, M, Andrews, I, Guerrini, R, Marini, C, Sadleir, LG, Berkovic, SF, Dibbens, LM, Scheffer, IE, Grinton, BE, Heron, SE, Kivity, S, Afawi, Z, Iona, X, Goldberg-Stern, H, Kinali, M, Andrews, I, Guerrini, R, Marini, C, Sadleir, LG, Berkovic, SF, and Dibbens, LM
Abstract: OBJECTIVE: Benign familial infantile epilepsy (BFIE) is an autosomal dominant epilepsy syndrome characterized by afebrile seizures beginning at about 6 months of age. Mutations in PRRT2, encoding the proline-rich transmembrane protein 2 gene, have recently been identified in the majority of families with BFIE and the associated syndrome of infantile convulsions and choreoathetosis (ICCA). We asked whether the phenotypic spectrum of PRRT2 was broader than initially recognized by studying patients with sporadic benign infantile seizures and non-BFIE familial infantile seizures for PRRT2 mutations. METHODS: Forty-four probands with infantile-onset seizures, infantile convulsions with mild gastroenteritis, and benign neonatal seizures underwent detailed phenotyping and PRRT2 sequencing. The familial segregation of mutations identified in probands was studied. RESULTS: The PRRT2 mutation c.649-650insC (p.R217fsX224) was identified in 11 probands. Nine probands had a family history of BFIE or ICCA. Two probands had no family history of infantile seizures or paroxysmal kinesigenic dyskinesia and had de novo PRRT2 mutations. Febrile seizures with or without afebrile seizures were observed in 2 families with PRRT2 mutations. CONCLUSIONS: PRRT2 mutations are present in >80% of BFIE and >90% ICCA families, but are not a common cause of other forms of infantile epilepsy. De novo mutations of PRRT2 can cause sporadic benign infantile seizures. Seizures with fever may occur in BFIE such that it may be difficult to distinguish BFIE from febrile seizures and febrile seizures plus in small families.
Published: 2012

256. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood

Author: Heinzen, EL, Swoboda, KJ, Hitomi, Y, Gurrieri, F, Nicole, S, de Vries, B, Tiziano, FD, Fontaine, B, Walley, NM, Heavin, S, Panagiotakaki, E, Fiori, S, Abiusi, E, Di Pietro, L, Sweney, MT, Newcomb, TM, Viollet, L, Huff, C, Jorde, LB, Reyna, SP, Murphy, KJ, Shianna, KV, Gumbs, CE, Little, L, Silver, K, Ptacek, LJ, Haan, J, Ferrari, MD, Bye, AM, Herkes, GK, Whitelaw, CM, Webb, D, Lynch, BJ, Uldall, P, King, MD, Scheffer, IE, Neri, G, Arzimanoglou, A, van den Maagdenberg, AMJM, Sisodiya, SM, Mikati, MA, Goldstein, DB, Heinzen, EL, Swoboda, KJ, Hitomi, Y, Gurrieri, F, Nicole, S, de Vries, B, Tiziano, FD, Fontaine, B, Walley, NM, Heavin, S, Panagiotakaki, E, Fiori, S, Abiusi, E, Di Pietro, L, Sweney, MT, Newcomb, TM, Viollet, L, Huff, C, Jorde, LB, Reyna, SP, Murphy, KJ, Shianna, KV, Gumbs, CE, Little, L, Silver, K, Ptacek, LJ, Haan, J, Ferrari, MD, Bye, AM, Herkes, GK, Whitelaw, CM, Webb, D, Lynch, BJ, Uldall, P, King, MD, Scheffer, IE, Neri, G, Arzimanoglou, A, van den Maagdenberg, AMJM, Sisodiya, SM, Mikati, MA, and Goldstein, DB
Abstract: Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurological manifestations. AHC is usually a sporadic disorder and has unknown etiology. We used exome sequencing of seven patients with AHC and their unaffected parents to identify de novo nonsynonymous mutations in ATP1A3 in all seven individuals. In a subsequent sequence analysis of ATP1A3 in 98 other patients with AHC, we found that ATP1A3 mutations were likely to be responsible for at least 74% of the cases; we also identified one inherited mutation in a case of familial AHC. Notably, most AHC cases are caused by one of seven recurrent ATP1A3 mutations, one of which was observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset dystonia-parkinsonism, AHC-causing mutations in this gene caused consistent reductions in ATPase activity without affecting the level of protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in ATP1A3.
Published: 2012

257. Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency

Author: Arsov, T, Mullen, SA, Damiano, JA, Lawrence, KM, Huh, LL, Nolan, M, Young, H, Thouin, A, Dahl, H-HM, Berkovic, SF, Crompton, DE, Sadleir, LG, Scheffer, IE, Arsov, T, Mullen, SA, Damiano, JA, Lawrence, KM, Huh, LL, Nolan, M, Young, H, Thouin, A, Dahl, H-HM, Berkovic, SF, Crompton, DE, Sadleir, LG, and Scheffer, IE
Abstract: Glucose transporter 1 (GLUT1) deficiency caused by mutations of SLC2A1 is an increasingly recognized cause of genetic generalized epilepsy. We previously reported that >10% (4 of 34) of a cohort with early onset absence epilepsy (EOAE) had GLUT1 deficiency. This study uses a new cohort of 55 patients with EOAE to confirm that finding. Patients with typical absence seizures beginning before 4 years of age were screened for solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) mutations or deletions. All had generalized spike-waves on electroencephalography (EEG). Those with tonic and/or atonic seizures were excluded. Mutations were found in 7 (13%) of 55 cases, including five missense mutations, an in-frame deletion leading to loss of a single amino acid, and a deletion spanning two exons. Over both studies, 11 (12%) of 89 probands with EOAE have GLUT1 deficiency. Given the major treatment and genetic counseling implications, this study confirms that SLC2A1 mutational analysis should be strongly considered in EOAE.
Published: 2012

258. The Role of Seizure-Related SEZ6 as a Susceptibility Gene in Febrile Seizures

Author: Mulley, JC, Iona, X, Hodgson, B, Heron, SE, Berkovic, SF, Scheffer, IE, Dibbens, LM, Mulley, JC, Iona, X, Hodgson, B, Heron, SE, Berkovic, SF, Scheffer, IE, and Dibbens, LM
Abstract: Sixty cases of febrile seizures from a Chinese cohort had previously been reported with a strong association between variants in the seizure-related (SEZ) 6 gene and febrile seizures. They found a striking lack of genetic variation in their controls. We found genetic variation in SEZ6 at similar levels at the same DNA sequence positions in our 94 febrile seizure cases as in our 96 unaffected controls. Two of our febrile seizure cases carried rare variants predicted to have damaging consequences. Combined with some of the variants from the Chinese cohort, these data are compatible with a role for SEZ6 as a susceptibility gene for febrile seizures. However, the polygenic determinants underlying most cases of febrile seizures with complex inheritance remain to be determined.
Published: 2011

259. Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology

Author: Catarino, CB, Liu, JYW, Liagkouras, I, Gibbons, VS, Labrum, RW, Ellis, R, Woodward, C, Davis, MB, Smith, SJ, Cross, JH, Appleton, RE, Yendle, SC, McMahon, JM, Bellows, ST, Jacques, TS, Zuberi, SM, Koepp, MJ, Martinian, L, Scheffer, IE, Thom, M, Sisodiya, SM, Catarino, CB, Liu, JYW, Liagkouras, I, Gibbons, VS, Labrum, RW, Ellis, R, Woodward, C, Davis, MB, Smith, SJ, Cross, JH, Appleton, RE, Yendle, SC, McMahon, JM, Bellows, ST, Jacques, TS, Zuberi, SM, Koepp, MJ, Martinian, L, Scheffer, IE, Thom, M, and Sisodiya, SM
Abstract: Dravet syndrome is an epilepsy syndrome of infantile onset, frequently caused by SCN1A mutations or deletions. Its prevalence, long-term evolution in adults and neuropathology are not well known. We identified a series of 22 adult patients, including three adult post-mortem cases with Dravet syndrome. For all patients, we reviewed the clinical history, seizure types and frequency, antiepileptic drugs, cognitive, social and functional outcome and results of investigations. A systematic neuropathology study was performed, with post-mortem material from three adult cases with Dravet syndrome, in comparison with controls and a range of relevant paediatric tissue. Twenty-two adults with Dravet syndrome, 10 female, were included, median age 39 years (range 20-66). SCN1A structural variation was found in 60% of the adult Dravet patients tested, including one post-mortem case with DNA extracted from brain tissue. Novel mutations were described for 11 adult patients; one patient had three SCN1A mutations. Features of Dravet syndrome in adulthood include multiple seizure types despite polytherapy, and age-dependent evolution in seizure semiology and electroencephalographic pattern. Fever sensitivity persisted through adulthood in 11 cases. Neurological decline occurred in adulthood with cognitive and motor deterioration. Dysphagia may develop in or after the fourth decade of life, leading to significant morbidity, or death. The correct diagnosis at an older age made an impact at several levels. Treatment changes improved seizure control even after years of drug resistance in all three cases with sufficient follow-up after drug changes were instituted; better control led to significant improvement in cognitive performance and quality of life in adulthood in two cases. There was no histopathological hallmark feature of Dravet syndrome in this series. Strikingly, there was remarkable preservation of neurons and interneurons in the neocortex and hippocampi of Dravet adult post-mo
Published: 2011

260. Autosomal dominant nocturnal frontal-lobe epilepsy : genetic heterogeneity and evidence for a second locus at 15q24

Author: Phillips, HA, Scheffer, IE, Crossland, KM, Phatia, KP, Fish, DR, Marsden, CD, Howell, SJL, Stephenson, JBP, Tolmie, J, Plazzi, G, Eeg-Olofsson, O, Singh, R, Lopes-Cendes, I, Andermann, E, Andermann, F, Berkovic, SF, Mulley, JC, Phillips, HA, Scheffer, IE, Crossland, KM, Phatia, KP, Fish, DR, Marsden, CD, Howell, SJL, Stephenson, JBP, Tolmie, J, Plazzi, G, Eeg-Olofsson, O, Singh, R, Lopes-Cendes, I, Andermann, E, Andermann, F, Berkovic, SF, and Mulley, JC
Published: 1998

261. PRRT2 phenotypic spectrum includes sporadic and fever-related infantile seizures.

Author: Scheffer IE, Grinton BE, Heron SE, Kivity S, Afawi Z, Iona X, Goldberg-Stern H, Kinali M, Andrews I, Guerrini R, Marini C, Sadleir LG, Berkovic SF, Dibbens LM, Scheffer, Ingrid E, Grinton, Bronwyn E, Heron, Sarah E, Kivity, Sara, Afawi, Zaid, and Iona, Xenia
Published: 2012
Full Text: View/download PDF

262. Peritrigonal and temporo-occipital heterotopia with corpus callosum and cerebellar dysgenesis.

Author: Pisano T, Barkovich AJ, Leventer RJ, Squier W, Scheffer IE, Parrini E, Blaser S, Marini C, Robertson S, Tortorella G, Rosenow F, Thomas P, McGillivray G, Andermann E, Andermann F, Berkovic SF, Dobyns WB, Guerrini R, Pisano, Tiziana, and Barkovich, A James
Published: 2012
Full Text: View/download PDF

263. De novo SCN1A mutations in migrating partial seizures of infancy.

Author: Carranza Rojo D, Hamiwka L, McMahon JM, Dibbens LM, Arsov T, Suls A, Stödberg T, Kelley K, Wirrell E, Appleton B, Mackay M, Freeman JL, Yendle SC, Berkovic SF, Bienvenu T, De Jonghe P, Thorburn DR, Mulley JC, Mefford HC, and Scheffer IE
Published: 2011
Full Text: View/download PDF

264. Recurrence risk of epilepsy and mental retardation in females due to parental mosaicism of PCDH19 mutations.

Author: Dibbens LM, Kneen R, Bayly MA, Heron SE, Arsov T, Damiano JA, Desai T, Gibbs J, McKenzie F, Mulley JC, Ronan A, and Scheffer IE
Published: 2011
Full Text: View/download PDF

265. Electroencephalographic abnormalities during sleep in children with developmental speech-language disorders: a case-control study.

Author: Parry-Fielder B, Collins K, Fisher J, Keir E, Anderson V, Jacobs R, Scheffer IE, and Nolan T
Abstract: Earlier research has suggested a link between epileptiform activity in the electroencephalogram (EEG) and developmental speech-language disorder (DSLD). This study investigated the strength of this association by comparing the frequency of EEG abnormalities in 45 language-normal children (29 males, 16 females; mean age 6y 11mo, SD 1y 10mo, range 4y-9y 10mo) and 54 community-ascertained children (35 males, 19 females; mean age 5y 7mo, SD 1y 6mo, range 4y-9y 11mo) with a diagnosis of severe DSLD, defined as a score at least 2 SD below the mean on at least one speech-language measure, and a performance IQ of at least 80 points. All participants underwent sleep EEGs after sedation. Children with DSLD also had detailed speech-language, hearing, and psychological assessments. Results failed to support the previously identified strong association between abnormal EEG and DSLD. There was a weak, non-significant relationship between DSLD and epileptiform EEG. Epileptiform EEG was significantly associated with low performance IQ (p=0.04). This study draws into question previously reported associations between epileptiform activity and DSLD probably because it examined a purer cohort of children with more severe language difficulties who did not have seizures. [ABSTRACT FROM AUTHOR]
Published: 2009
Full Text: View/download PDF

266. Reduced striatal D1 receptor binding in autosomal dominant nocturnal frontal lobe epilepsy.

Author: Fedi M, Berkovic SF, Scheffer IE, O'Keefe G, Marini C, Mulligan R, Gong S, Tochon-Danguy H, and Reutens DC
Published: 2008
Full Text: View/download PDF

267. Vaccination, seizures and 'vaccine damage'.

Author: Brown NJ, Berkovic SF, and Scheffer IE
Published: 2007
Full Text: View/download PDF

268. Genetic dissection of the common epilepsies.

Author: Tan NCK, Mulley JC, and Scheffer IE
Published: 2006
Full Text: View/download PDF

269. Familial clustering of seizure types within the idiopathic generalized epilepsies.

Author: Winawer MR, Marini C, Grinton BE, Rabinowitz D, Berkovic SF, Scheffer IE, Ottman R, Winawer, M R, Marini, C, Grinton, B E, Rabinowitz, D, Berkovic, S F, Scheffer, I E, and Ottman, R
Published: 2005
Full Text: View/download PDF

270. Juvenile myoclonic epilepsy and idiopathic photosensitive occipital lobe epilepsy: is there overlap?

Author: Taylor I, Marini C, Johnson MR, Turner S, Berkovic SF, and Scheffer IE
Published: 2004

271. Is benign rolandic epilepsy genetically determined?

Author: Vadlamudi L, Harvey AS, Connellan MM, Milne RL, Hopper JL, Scheffer IE, and Berkovic SF
Published: 2004

272. Epilepsy in 2012: Advances in epilepsy shed light on key questions.

Author: Scheffer IE, Mullen SA, Scheffer, Ingrid E, and Mullen, Saul A
Abstract: Research on epilepsies in 2012 has substantially advanced our knowledge of these often devastating conditions. From important discoveries that revealed causative factors and the molecular basis of disease, to major implications for surgical decision-making, these studies set the scene for future advances in the field. [ABSTRACT FROM AUTHOR]
Published: 2013
Full Text: View/download PDF

273. Lack of replication of association between scn1a SNP and febrile seizures.

Author: Petrovski S, Scheffer IE, Sisodiya SM, O'Brien TJ, Berkovic SF, EPIGEN Consortium, Petrovski, S, Scheffer, I E, Sisodiya, S M, O'Brien, T J, and Berkovic, S F
Published: 2009
Full Text: View/download PDF

274. Severe myoclonic epilepsy of infancy (Dravet syndrome): recognition and diagnosis in adults.

Author: Jansen FE, Sadleir LG, Harkin LA, Vadlamudi L, McMahon JM, Mulley JC, Scheffer IE, and Berkovic SF
Published: 2006
Full Text: View/download PDF

275. GLUT1 deficiency: A glut of epilepsy phenotypes.

Author: Scheffer IE
Published: 2012
Full Text: View/download PDF

276. Does genotype determine phenotype?: Sodium channel mutations in Dravet syndrome and GEFS+.

Author: Scheffer IE
Published: 2011
Full Text: View/download PDF

277. Copy number variants--an unexpected risk factor for the idiopathic generalized epilepsies.

Author: Scheffer IE and Berkovic SF
Published: 2010
Full Text: View/download PDF

278. A new molecular mechanism for severe myoclonic epilepsy of infancy: exonic deletions in SCN1A.

Author: Mulley JC, Nelson P, Guerrero S, Dibbens L, Iona X, McMahon JM, Harkin L, Schouten J, Yu S, Berkovic SF, and Scheffer IE
Published: 2006
Full Text: View/download PDF

279. Amygdala dysplasia with temporal lobe epilepsy and obsessive-compulsive disorder: an fMRI/EEG study.

Author: Labate A, Briellmann RS, Scheffer IE, Waites AB, Kalnins RM, Jackson GD, Labate, A, Briellmann, R S, Scheffer, I E, Waites, A B, Kalnins, R M, and Jackson, G D
Published: 2005
Full Text: View/download PDF

280. Genetic influence on rolandic epilepsy.

Author: Bali B, Kugler SL, Pal DK, Vadlamudi L, Harvey AS, Hopper JL, Scheffer IE, and Berkovic SF
Published: 2005

281. Epileptiform EEG abnormalities in children with language regression.

Author: Scheffer IE, Parry-Fielder B, Mullen SA, and Saunders K
Published: 2006
Full Text: View/download PDF

282. Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes

Author: Scheffer, IE and Berkovic, SF
Published: 1997
Full Text: View/download PDF

283. Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental and epileptic encephalopathies: 27 new patients and overview of the literature

Author: Delphine Breuillard, Isabelle Marey, Claire Bar, Tayeb Sekhara, Candace T. Myers, Diane Doummar, Alice Poisson, Hervé Isnard, Nathalie Dorison, Gwenaël Le Guyader, Arnold Munnich, Alexandra Afenjar, Anne de Saint Martin, Jamel Chelly, Gaetan Lesca, Gaetano Terrone, Rima Nabbout, Jeremy L. Freeman, David Geneviève, Sophie Dupont, Cyril Mignot, Katherine B. Howell, Giulia Barcia, Melanie Jennesson, Patrick Berquin, Sylvie Odent, Boris Keren, Ingrid E. Scheffer, Renzo Guerrini, Emmanuel Scalais, Thierry Billette de Villemeur, Martino Montomoli, Agnès Guët, Pierre Meyer, Anca Nica, Anne-Sophie Lebre, Edor Kabashi, Carla Marini, Amy L Schneider, Marion Gérard, Salima El Chehadeh, Heather C Mefford, Lynette G. Sadleir, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), American Memorial Hospital, Centre hospitalier universitaire de Poitiers (CHU Poitiers), University of Melbourne, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), A Meyer Children's Hospital, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Equipe NEMESIS - Centre de Recherches de l'Institut du Cerveau et de la Moelle épinière (NEMESIS-CRICM), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Amiens-Picardie, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Hôpital de Hautepierre [Strasbourg], Hôpitaux Universitaires de Strasbourg, Hôpital Louis-Mourier, Colombes, France., Centre Hospitalier de Luxembourg [Luxembourg] (CHL), Rothschild Foundation Hospital, Paris., University of Washington [Seattle], Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia., A.Meyer Children's Hospital, CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Section of Pediatrics-Child Neurology Unit, Federico II University, 80131, Naples, Italy, Centre Hospitalier Interrégional Edith Cavell (CHIREC), Service de génétique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CLAD-Ouest, CHU Rennes, France., University of Otago [Dunedin, Nouvelle-Zélande], Pediatric Neurology & Neurogenetics Unit and Laboratories, Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Children's Hospital A. Meyer, Epilepsy Research Centre, The Florey Institute of Neurosciences and Mental Health, Heidelberg, Victoria, Australia., Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Centre de référence des épilepsies rares [CHU Pitié-Salpêtrière], Unité fonctionnelle d'épilepsie [CHU Pitié-Salpêtrière], Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-IFR70-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Service de Neurologie [CHU Pitié-Salpêtrière], H2020 European Research Council, Health Research Council of New Zealand, Agence Nationale de la Recherche, Seventh Framework Programme, Fondation Bettencourt Schueller, European Research Council, Bar, C, Barcia, G, Jennesson, M, Le Guyader, G, Schneider, A, Mignot, C, Lesca, G, Breuillard, D, Montomoli, M, Keren, B, Doummar, D, de Villemeur, Tb, Afenjar, A, Marey, I, Gerard, M, Isnard, H, Poisson, A, Dupont, S, Berquin, P, Meyer, P, Genevieve, D, De Saint Martin, A, El Chehadeh, S, Chelly, J, Guët, A, Scalais, E, Dorison, N, Myers, Ct, Mefford, Hc, Howell, Kb, Marini, C, Freeman, Jl, Nica, A, Terrone, G, Sekhara, T, Lebre, A, Odent, S, Sadleir, Lg, Munnich, A, Guerrini, R, Scheffer, Ie, Kabashi, E, Nabbout, R, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [APHP], Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Hôpital Armand Trousseau, Hôpital Armand Trousseau, Paris, France., Centre de Référence déficiences intellectuelles de causes rares, GH Pitie-Salpêtrière-Charles Foix, F-, 75013, Paris, France., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Centre Hospitalier de Luxembourg, C.H.I.R.E.C, Brussels, Belgium., Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Children's Hospital A. Meyer-University of Florence (UNIFI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (ISC-MJ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Naples Federico II = Università degli studi di Napoli Federico II, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Università degli Studi di Firenze = University of Florence (UniFI)-Children's Hospital A. Meyer, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Children's Hospital A. Meyer-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-IFR70-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Service de Neurologie [CHU Pitié-Salpêtrière]
Subjects: Genotype, [SDV]Life Sciences [q-bio], Biology, Structure-Activity Relationship, 03 medical and health sciences, Epilepsy, Shab Potassium Channels, KCNB1, Intellectual disability, Genetic variation, Genetics, medicine, Humans, Missense mutation, Genetic Predisposition to Disease, Allele, developmental and epileptic encephalopathy, Alleles, Genetic Association Studies, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, 030305 genetics & heredity, Genetic Variation, medicine.disease, Axon initial segment, Phenotype, Neurodevelopmental Disorders, epilepsy, potassium channel
Abstract: International audience; Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the alpha subunit of the delayed-rectifier voltage-dependent potassium channel Kv 2.1. We review the 37 previously reported patients carrying 29 distinct KCNB1 variants and significantly expand the mutational spectrum describing 18 novel variants from 27 unreported patients. Most variants occur de novo and mainly consist of missense variants located on the voltage sensor and the pore domain of Kv 2.1. We also report the first inherited variant (p.Arg583*). KCNB1-related encephalopathies encompass a wide spectrum of neurodevelopmental disorders with predominant language difficulties and behavioral impairment. Eighty-five percent of patients developed epilepsies with variable syndromes and prognosis. Truncating variants in the C-terminal domain are associated with a less severe epileptic phenotype. Overall, this report provides an up-to-date review of the mutational and clinical spectrum of KCNB1, strengthening its place as a causal gene in DEEs and emphasizing the need for further functional studies to unravel the underlying mechanisms.
Published: 2020

284. Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3

Author: Florian R. T., Kraft F., Leitao E., Kaya S., Klebe S., Magnin E., van Rootselaar A. -F., Buratti J., Kuhnel T., Schroder C., Giesselmann S., Tschernoster N., Altmueller J., Lamiral A., Keren B., Nava C., Bouteiller D., Forlani S., Jornea L., Kubica R., Ye T., Plassard D., Jost B., Meyer V., Deleuze J. -F., Delpu Y., Avarello M. D. M., Vijfhuizen L. S., Rudolf G., Hirsch E., Kroes T., Reif P. S., Rosenow F., Ganos C., Vidailhet M., Thivard L., Mathieu A., Bourgeron T., Kurth I., Rafehi H., Steenpass L., Horsthemke B., Berkovic S. F., Bisulli F., Brancati F., Canafoglia L., Casari G., Guerrini R., Ishiura H., Licchetta L., Mei D., Pippucci T., Sadleir L., Scheffer I. E., Striano P., Tinuper P., Tsuji S., Zara F., LeGuern E., Klein K. M., Labauge P., Bennett M. F., Bahlo M., Gecz J., Corbett M. A., Tijssen M. A. J., van den Maagdenberg A. M. J. M., Depienne C., Florian, R. T., Kraft, F., Leitao, E., Kaya, S., Klebe, S., Magnin, E., van Rootselaar, A. -F., Buratti, J., Kuhnel, T., Schroder, C., Giesselmann, S., Tschernoster, N., Altmueller, J., Lamiral, A., Keren, B., Nava, C., Bouteiller, D., Forlani, S., Jornea, L., Kubica, R., Ye, T., Plassard, D., Jost, B., Meyer, V., Deleuze, J. -F., Delpu, Y., Avarello, M. D. M., Vijfhuizen, L. S., Rudolf, G., Hirsch, E., Kroes, T., Reif, P. S., Rosenow, F., Ganos, C., Vidailhet, M., Thivard, L., Mathieu, A., Bourgeron, T., Kurth, I., Rafehi, H., Steenpass, L., Horsthemke, B., Berkovic, S. F., Bisulli, F., Brancati, F., Canafoglia, L., Casari, G., Guerrini, R., Ishiura, H., Licchetta, L., Mei, D., Pippucci, T., Sadleir, L., Scheffer, I. E., Striano, P., Tinuper, P., Tsuji, S., Zara, F., Leguern, E., Klein, K. M., Labauge, P., Bennett, M. F., Bahlo, M., Gecz, J., Corbett, M. A., Tijssen, M. A. J., van den Maagdenberg, A. M. J. M., Depienne, C., Institute of Human Genetics - Institut für Humangenetik [Essen], Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen)-Universitat Duisberg-Essen, Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Universität Duisburg-Essen = University of Duisburg-Essen [Essen], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), Amsterdam Neuroscience [Pays-Bas], Vrije Universiteit Amsterdam [Amsterdam] (VU)-University of Amsterdam [Amsterdam] (UvA)-VU University Medical Center [Amsterdam], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre for Molecular Medicine Cologne [Cologne] (CMMC), University Hospital of Cologne [Cologne], Cologne Center for Genomics [Cologne] (CCG), University of Cologne, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), genomic vision, Leiden University Medical Center (LUMC), Universiteit Leiden, Centre de référence des épilepsies rares [CHRU Strasbourg] (CRéER), Centre Hospitalier Régional Universitaire de Strasbourg (CHRU de Strasbourg), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, School of Biological Sciences [Adelaïde], University of Adelaide, Goethe-University Frankfurt am Main, Philipps Universität Marburg = Philipps University of Marburg, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Epilepsy Research Centre, University of Calgary, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), South Australian Health and Medical Research Institute [ Adelaide] (SAHMRI), University Medical Center Groningen [Groningen] (UMCG), This study has been financially supported by three different grants from the Fondation Maladies rares to C.D. (2009, 2010, 2016), Assistance Publique des Hôpitaux de Paris (APHP), INSERM, the 'Investissements d’Avenir' programme ANR-10-IAIHU-06 (IHU-A-ICM), University Duisburg-Essen and University Hospital Essen. M.B. was supported by an Australian National Health and Medical Research Council (NHMRC) Program Grant (GNT1054618) and an NHMRC Senior Research Fellowship (GNT1102971). This work was also supported by the Victorian Government’s Operational Infrastructure Support Program and the NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS). Laura Canafoglia: Member of the European Reference Network on Rare and Complex epilepsies, ERN EpiCARE., We thank the families for their participation in this study, Agnès Rastetter (ICM, Paris, France) for RNA extraction, and Emmanuelle Apartis (Hôpital Saint-Antoine, Paris, France) for electrophysiological assessment of Family 1. DNA extraction and cell culture of lymphoblasts have been performed at the DNA and cell bank of ICM (Paris, France). RNA-seq has been performed on the GenomEast platform of IGBMC, Illkirch, France. WGS has been performed by the Centre National de Recherche en Génomique Humaine (CNRGH) Institut de Biologie François Jacob, Evry, France. We thank Jean-Louis Mandel and Nicolas Charlet-Berguerand (IGBMC, Strasbourg, France), Cécile Cazeneuve (Hôpital Pitié-Salpêtrière, Paris, France), Charles Marcaillou (Integragen, Evry, France) and Isabel Silveira (Porto, Portugal) for valuable discussions., FAME consortium : Berkovic SF, Bisulli F, Brancati F, Canafoglia L, Casari G, Guerrini R, Ishiura H, Licchetta L, Mei D, Pippucci T, Sadleir L, Scheffer IE, Striano P, Tinuper P, Tsuji S, Zara F., Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Recherche en Génomique Humaine (CNRGH), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), RWTH Aachen University, Universität Duisburg-Essen [Essen], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Philipps University of Marburg, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]-Université de Paris (UP), Hôpital Gui de Chauliac, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Rahel T. Florian, Florian Kraft, Elsa Leitão, Sabine Kaya, Stephan Klebe, Eloi Magnin, Anne-Fleur van Rootselaar, Julien Buratti, Theresa Kühnel, Christopher Schröder, Sebastian Giesselmann, Nikolai Tschernoster, Janine Altmueller, Anaide Lamiral, Boris Keren, Caroline Nava, Delphine Bouteiller, Sylvie Forlani, Ludmila Jornea, Regina Kubica, Tao Ye, Damien Plassard, Bernard Jost, Vincent Meyer, Jean-François Deleuze, Yannick Delpu, Mario D.M. Avarello, Lisanne S. Vijfhuizen, Gabrielle Rudolf, Edouard Hirsch, Thessa Kroes, Philipp S. Reif, Felix Rosenow, Christos Ganos, Marie Vidailhet, Lionel Thivard, Alexandre Mathieu, Thomas Bourgeron, Ingo Kurth, Haloom Rafehi, Laura Steenpass, Bernhard Horsthemke, FAME consortium, Eric LeGuern, Karl Martin Klein, Pierre Labauge, Mark F. Bennett, Melanie Bahlo, Jozef Gecz, Mark A. Corbett, Marina A.J. Tijssen, Arn M.J.M. van den Maagdenberg, Christel Depienne, Francesca Bisulli, Laura Licchetta, Paolo Tinuper, MATHIEU, Alexandre, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: Male, MESH: Introns, [SDV]Life Sciences [q-bio], Medizin, MESH: DNA Repeat Expansion, Epilepsies, Myoclonic, [SDV.GEN] Life Sciences [q-bio]/Genetics, MARCH6, expansion, MESH: Ubiquitin-Protein Ligases/genetics, MESH: Aged, MESH: Middle Aged, DNA Repeat Expansion, Neurodegenerative diseases, MESH: Epilepsies, Myoclonic, Chromosome Mapping, Middle Aged, MESH: Epilepsies, Myoclonic/genetics, Pedigree, MESH: Young Adult, Female, ddc:500, MESH: Membrane Proteins, Technology Platforms, Genomic instability, Adult, Adolescent, MESH: Pedigree, Ubiquitin-Protein Ligases, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Familial Adult Myoclonic Epilepsy type 3, Article, Young Adult, Humans, Aged, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, Epilepsy, Membrane Proteins, MESH: Adult, MESH: Membrane Proteins/genetics, MESH: Ubiquitin-Protein Ligases, MESH: Male, Introns, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Chromosome Mapping, MESH: Female, Neurological disorders
Abstract: Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements., Familial cortical myoclonic tremor with epilepsy (FAME) is a slowly progressing cortical tremor mapping to various genomic loci, including intronic expansions in SAMD12 for FAME1. Here, Florian et al. describe mixed intronic TTTTA/TTTCA expansions of various lengths in the first intron of MARCH6 as a cause of FAME3.
Published: 2019

285. The epileptology of GNB5 encephalopathy

Author: Giuseppe Merla, Alison M. Muir, Boris Keren, Natascia Malerba, Chontelle King, Ingrid E. Scheffer, Peter Kannu, Brian H.Y. Chung, Gemma Poke, Mahendranath Moharir, Michele Germano, Carolina Fischinger Moura de Souza, Jasmine L.F. Fung, Guillem de Valles-Ibáñez, Heather C Mefford, Thorsten Stanley, Lynette G. Sadleir, Zhuo Shao, Anne Isabelle Vermersch, Cyril Mignot, Adina Ilea, Cheuk Wing Fung, Suzanne Davis, Poke, G., King, C., Muir, A., de Valles Ibáñez, G., Germano, M., de Souza, C., Fung, J., Chung, B., Fung, Cw, Mignot, C., Ilea, A., Keren, B., Davis, S., Stanley, T., Moharir, M., Kannu, P., Shao, Z., Malerba, N., Merla, G, Mefford, Hc, Scheffer, Ie, and Sadleir, Lg.
Subjects: 0301 basic medicine, Male, Pediatrics, medicine.medical_specialty, Adolescent, Encephalopathy, 03 medical and health sciences, Epilepsy, Young Adult, 0302 clinical medicine, medicine, Humans, Child, Cerebral atrophy, Brain Diseases, business.industry, GTP-Binding Protein beta Subunits, medicine.disease, Hypotonia, Hypsarrhythmia, Pedigree, Epileptic spasms, Burst suppression, 030104 developmental biology, Neurology, Child, Preschool, Cerebellar atrophy, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Pathogenic variants in GNB5 cause an autosomal recessive neurodevelopmental disorder with neonatal sinus bradycardia. Seizures or epilepsy occurred in 10 of 22 previously reported cases, including 6 children from one family. We delineate the epileptology of GNB5 encephalopathy. Our nine patients, including five new patients, were from seven families. Epileptic spasms were the most frequent seizure type, occurring in eight of nine patients, and began at a median age of 3 months (2 months to 3 years). Focal seizures preceded spasms in three children, with onset at 7 days, 11 days, and 4 months. One child presented with convulsive status epilepticus at 6 months. Three children had burst suppression on electroencephalography (EEG), three had hypsarrhythmia, and one evolved from burst suppression to hypsarrhythmia. Background slowing was present in all after age 3 years. Magnetic resonance imaging (MRI) showed cerebral atrophy in one child and cerebellar atrophy in another. All nine had abnormal development prior to seizure onset and ultimately had profound impairment without regression. Hypotonia was present in all, with contractures developing in two older patients. All individuals had biallelic pathogenic variants in GNB5, predicted by in silico tools to result in protein truncation and loss-of-function. GNB5 developmental and epileptic encephalopathy is characterized by epileptic spasms, focal seizures, and profound impairment. Wiley Periodicals, Inc. © 2019 International League Against Epilepsy
Published: 2019

286. AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders

Author: Vincenzo Salpietro1, 2 3, 140, Christine L. Dixon4, Hui Guo5, 6 140, Oscar D. Bello Stephanie Efthymiou 1, 4, Reza Maroofian1, Gali Heimer7, Lydie Burglen 8, Stephanie Valence 9, Erin Torti 10, Moritz Hacke11, Julia Rankin12, Huma Tariq1, Estelle Colin13, Vincent Procaccio13, Pasquale Striano2, 3, Kshitij Mankad15, Andreas Lieb 4, Sharon Chen16, Laura Pisani16, Conceicao Bettencourt 17, Roope Männikkö 1, Andreea Manole1, Alfredo Brusco 18, Enrico Grosso18, Giovanni Battista Ferrero19, Judith Armstrong-Moron20, Sophie Gueden21, Omer Bar-Yosef7, Michal Tzadok7, Kristin G. Monaghan10, Teresa Santiago-Sim10, Richard E. Person10, Megan T. Cho10, Rebecca Willaert10, Yongjin Yoo22, Jong-Hee Chae23, Yingting Quan6, Huidan Wu6, Tianyun Wang5, 6, Raphael A. Bernier24, Kun Xia6, Alyssa Blesson25, Mahim Jain25, Mohammad M. Motazacker26, Bregje Jaeger27, Amy L. Schneider 28, Katja Boysen28, Alison M. Muir 29, Candace T. Myers30, Ralitza H. Gavrilova31, Lauren Gunderson31, Laura Schultz-Rogers 31, Eric W. Klee31, David Dyment32, Matthew Osmond32, 33 34, Mara Parellada35, Cloe Llorente36, Javier Gonzalez-Peñas37, Angel Carracedo38, Arie Van Haeringen40, Claudia Ruivenkamp40, Caroline Nava41, Delphine Heron41, Rosaria Nardello42, Michele Iacomino43, Carlo Minetti2, Aldo Skabar44, Antonella Fabretto44, SYNAPS Study GroupMiquel Raspall-Chaure45, Michael Chez46, Anne Tsai47, Emily Fassi48, Marwan Shinawi48, John N. Constantino49, Rita De Zorzi50, Sara Fortuna 50, Fernando Kok51, Boris Keren41, Dominique Bonneau13, Murim Choi 22, Bruria Benzeev7, Federico Zara43, Heather C. Mefford29, Ingrid E. Scheffer28, Jill Clayton-Smith53, Alfons Macaya45, James E. Rothman4, Evan E. Eichler 5, Dimitri M. Kullmann 4, Henry Houlden 1, SYNAPS Study Group Michael G. Hanna1, Enrico Bugiardini1, Isabel Hostettler1, Benjamin O’Callaghan1, Alaa Khan1, Andrea Cortese1, Emer O’Connor1, Wai Y. Yau1, Thomas Bourinaris1, Rauan Kaiyrzhanov1, Viorica Chelban1, Monika Madej1, Maria C. Diana2, Maria S. Vari2, Marina Pedemonte2, Claudio Bruno2, Ganna Balagura3, Marcello Scala3, Chiara Fiorillo3, Lino Nobili3, Nancy T. Malintan4, Maria N. Zanetti4, Shyam S. Krishnakumar4, Gabriele Lignani4, James E. C. Jepson4, Paolo Broda43, Simona Baldassari43, Pia Rossi43, Floriana Fruscione43, Francesca Madia43, Monica Traverso43, Patrizia De-Marco43, Belen Pérez-Dueñas45, Francina Munell45, Yamna Kriouile57, Mohamed El-Khorassani57, Blagovesta Karashova58, Daniela Avdjieva58, Hadil Kathom58, Radka Tincheva58, Lionel Van-Maldergem59, Wolfgang Nachbauer60, Sylvia Boesch60, Antonella Gagliano61, Elisabetta Amadori62, Jatinder S. Goraya63, Tipu Sultan64, Salman Kirmani65, Shahnaz Ibrahim66, Farida Jan66, Jun Mine67, Selina Banu68, Pierangelo Veggiotti69, Gian V. Zuccotti69, Michel D. Ferrari70, Arn M. J. Van Den Maagdenberg70, Alberto Verrotti71, Gian L. Marseglia72, Salvatore Savasta72, Miguel A. Soler73, Carmela Scuderi74, Eugenia Borgione74, Roberto Chimenz75, Eloisa Gitto75, Valeria Dipasquale75, Alessia Sallemi75, Monica Fusco75, Caterina Cuppari75, Maria C. Cutrupi75, Martino Ruggieri76, Armando Cama77, Valeria Capra77, Niccolò E. Mencacci78, Richard Boles79, Neerja Gupta80, Madhulika Kabra80, Savvas Papacostas81, Eleni Zamba-Papanicolaou81, Efthymios Dardiotis82, Shazia Maqbool83, Nuzhat Rana84, Osama Atawneh85, Shen Y. Lim86, Farooq Shaikh87, George Koutsis88, Marianthi Breza88, Domenico A. Coviello89, Yves A. Dauvilliers90, Issam AlKhawaja91, Mariam AlKhawaja92, Fuad Al-Mutairi93, Tanya Stojkovic94, Veronica Ferrucci, Massimo Zollo, Fowzan S. Alkuraya96, Maria Kinali97, Hamed Sherifa98, Hanene Benrhouma99, Ilhem B. Y. Turki99, Meriem Tazir100, Makram Obeid101, Sophia Bakhtadze102, Nebal W. Saadi103, Maha S. Zaki104, Chahnez C. Triki105, Fabio Benfenati106, Stefano Gustincich106, Majdi Kara107, Vincenzo Belcastro108, Nicola Specchio109, Giuseppe Capovilla110, Ehsan G. Karimiani111, Ahmed M. Salih112, Njideka U. Okubadejo113, Oluwadamilola O. Ojo113, Olajumoke O. Oshinaike113, Olapeju Oguntunde113, Kolawole Wahab114, Abiodun H. Bello114, Sanni Abubakar115, Yahaya Obiabo116, Ernest Nwazor117, Oluchi Ekenze118, Uduak Williams119, Alagoma Iyagba120, Lolade Taiwo121, Morenikeji Komolafe122, Konstantin Senkevich123, Chingiz Shashkin124, Nazira Zharkynbekova125, Kairgali Koneyev126, Ganieva Manizha127, Maksud Isrofilov127, Ulviyya Guliyeva128, Kamran Salayev129, Samson Khachatryan130, Salvatore Rossi131, Gabriella Silvestri131, Nourelhoda Haridy132, Luca A. Ramenghi133, Georgia Xiromerisiou134, Emanuele David135, Mhammed Aguennouz136, Liana Fidani137, Cleanthe Spanaki138, Arianna Tucci139, University College of London [London] (UCL), Instituto Giannina Gaslini, Genoa, University of Genoa (UNIGE), University of Washington [Seattle], Institute of Neurology, Queen Square, London, King‘s College London, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, London, Molecular and Clinical Sciences Institute - St George’s [London, UK] (Genetics Research Centre), University of London [London], Tel Aviv University Sackler School of Medicine [Tel Aviv, Israël], Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), GeneDx [Gaithersburg, MD, USA], Heidelberg University Hospital [Heidelberg], Royal Devon and Exeter NHS Foundation Trust [UK], Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Universita degli studi di Genova, Great Ormond Street Hospital for Children [London] (GOSH), The University of Sydney, Hofstra University [Hempstead], Università degli studi di Torino (UNITO), Hospital Sant Joan de Déu [Barcelona], Safra Children's Hospital, Seoul National University Hospital, Central South University [Changsha], Kennedy Krieger Institute [Baltimore], University of Amsterdam [Amsterdam] (UvA), University of Melbourne, Mayo Clinic [Rochester], Department of Health Sciences Research [Mayo Clinic] (HSR), Mayo Clinic, University of Ottawa [Ottawa], University of British Columbia (UBC), Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universidade de Santiago de Compostela [Spain] (USC ), Universiteit Leiden [Leiden], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli studi di Palermo - University of Palermo, University of Trieste, Universitat Autònoma de Barcelona (UAB), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), University of California-University of California, Children’s Hospital Colorado, University of Colorado Anschutz [Aurora], Washington University in Saint Louis (WUSTL), Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Department of Psychiatry, Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, University of Oxford [Oxford], University of São Paulo (USP), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Service de Pédiatrie, CHUR Poitiers, Seoul National University [Seoul] (SNU), Pediatric Neurology and Neuromuscular Diseases Unit, University of Manchester [Manchester], Yale University School of Medicine, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Salvy-Córdoba, Nathalie, Università degli studi di Genova = University of Genoa (UniGe), Tel Aviv University (TAU), Università degli studi di Torino = University of Turin (UNITO), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Trieste = University of Trieste, University of California (UC)-University of California (UC), University of Oxford, Universidade de São Paulo = University of São Paulo (USP), Yale School of Medicine [New Haven, Connecticut] (YSM), Salpietro V, Dixon CL, Guo H, Bello OD, Vandrovcova J, Efthymiou S, Maroofian R, Heimer G, Burglen L, Valence S, Torti E, Hacke M, Rankin J, Tariq H, Colin E, Procaccio V, Striano P, Mankad K, Lieb A, Chen S, Pisani L, Bettencourt C, Männikkö R, Manole A, Brusco A, Grosso E, Ferrero GB, Armstrong-Moron J, Gueden S, Bar-Yosef O, Tzadok M, Monaghan KG, Santiago-Sim T, Person RE, Cho MT, Willaert R, Yoo Y, Chae JH, Quan Y, Wu H, Wang T, Bernier RA, Xia K, Blesson A, Jain M, Motazacker MM, Jaeger B, Schneider AL, Boysen K, Muir AM, Myers CT, Gavrilova RH, Gunderson L, Schultz-Rogers L, Klee EW, Dyment D, Osmond M, Parellada M, Llorente C, Gonzalez-Peñas J, Carracedo A, Van Haeringen A, Ruivenkamp C, Nava C, Heron D, Nardello R, Iacomino M, Minetti C, Skabar A, Fabretto A, SYNAPS Study Group, Raspall-Chaure M, Chez M, Tsai A, Fassi E, Shinawi M, Constantino JN, De Zorzi R, Fortuna S, Kok F, Keren B, Bonneau D, Choi M, Benzeev B, Zara F, Mefford HC, Scheffer IE, Clayton-Smith J, Macaya A, Rothman JE, Eichler EE, Kullmann DM, Houlden H, Salpietro, Vincenzo, Dixon, Christine L, Guo, Hui, Bello, Oscar D, Vandrovcova, Jana, Efthymiou, Stephanie, Maroofian, Reza, Heimer, Gali, Burglen, Lydie, Valence, Stephanie, Torti, Erin, Hacke, Moritz, Rankin, Julia, Tariq, Huma, Colin, Estelle, Procaccio, Vincent, Striano, Pasquale, Mankad, Kshitij, Lieb, Andrea, Chen, Sharon, Pisani, Laura, Bettencourt, Conceicao, Männikkö, Roope, Manole, Andreea, Brusco, Alfredo, Grosso, Enrico, Ferrero, Giovanni Battista, Armstrong-Moron, Judith, Gueden, Sophie, Bar-Yosef, Omer, Tzadok, Michal, Monaghan, Kristin G, Santiago-Sim, Teresa, Person, Richard E, Cho, Megan T, Willaert, Rebecca, Yoo, Yongjin, Chae, Jong-Hee, Quan, Yingting, Wu, Huidan, Wang, Tianyun, Bernier, Raphael A, Xia, Kun, Blesson, Alyssa, Jain, Mahim, Motazacker, Mohammad M, Jaeger, Bregje, Schneider, Amy L, Boysen, Katja, Muir, Alison M, Myers, Candace T, Gavrilova, Ralitza H, Gunderson, Lauren, Schultz-Rogers, Laura, Klee, Eric W, Dyment, David, Osmond, Matthew, Parellada, Mara, Llorente, Cloe, Gonzalez-Peñas, Javier, Carracedo, Angel, Van Haeringen, Arie, Ruivenkamp, Claudia, Nava, Caroline, Heron, Delphine, Nardello, Rosaria, Iacomino, Michele, Minetti, Carlo, Skabar, Aldo, Fabretto, Antonella, Raspall-Chaure, Miquel, Chez, Michael, Tsai, Anne, Fassi, Emily, Shinawi, Marwan, Constantino, John N, De Zorzi, Rita, Fortuna, Sara, Kok, Fernando, Keren, Bori, Bonneau, Dominique, Choi, Murim, Benzeev, Bruria, Zara, Federico, Mefford, Heather C, Scheffer, Ingrid E, Clayton-Smith, Jill, Macaya, Alfon, Rothman, James E, Eichler, Evan E, Kullmann, Dimitri M, Houlden, Henry, Salpietro1, Vincenzo, 3, 2, Dixon4, Christine L., Guo5, Hui, 140, 6, Bello Stephanie Efthymiou 1, Oscar D., Maroofian1, Reza, Heimer7, Gali, 8, Lydie Burglen, 9, Stephanie Valence, Torti 10, Erin, Hacke11, Moritz, Rankin12, Julia, Tariq1, Huma, Colin13, Estelle, Procaccio13, Vincent, Striano2, Pasquale, Mankad15, Kshitij, 4, Andreas Lieb, Chen16, Sharon, Pisani16, Laura, Bettencourt 17, Conceicao, 1, Roope Männikkö, Manole1, Andreea, Brusco 18, Alfredo, Grosso18, Enrico, Battista Ferrero19, Giovanni, Armstrong-Moron20, Judith, Gueden21, Sophie, Bar-Yosef7, Omer, Tzadok7, Michal, Monaghan10, Kristin G., Santiago-Sim10, Teresa, Person10, Richard E., Cho10, Megan T., Willaert10, Rebecca, Yoo22, Yongjin, Chae23, Jong-Hee, Quan6, Yingting, Wu6, Huidan, Wang5, Tianyun, Bernier24, Raphael A., Xia6, Kun, Blesson25, Alyssa, Jain25, Mahim, Motazacker26, Mohammad M., Jaeger27, Bregje, Schneider 28, Amy L., Boysen28, Katja, Muir 29, Alison M., Myers30, Candace T., Gavrilova31, Ralitza H., Gunderson31, Lauren, Schultz-Rogers 31, Laura, Klee31, Eric W., Dyment32, David, Osmond32, Matthew, 34, 33, Parellada35, Mara, Llorente36, Cloe, Gonzalez-Peñas37, Javier, Carracedo38, Angel, Van Haeringen40, Arie, Ruivenkamp40, Claudia, Nava41, Caroline, Heron41, Delphine, Nardello42, Rosaria, Iacomino43, Michele, Minetti2, Carlo, Skabar44, Aldo, Fabretto44, Antonella, Study GroupMiquel Raspall-Chaure45, Synap, Chez46, Michael, Tsai47, Anne, Fassi48, Emily, Shinawi48, Marwan, Constantino49, John N., De Zorzi50, Rita, Fortuna 50, Sara, Kok51, Fernando, Keren41, Bori, Bonneau13, Dominique, Choi 22, Murim, Benzeev7, Bruria, Zara43, Federico, Mefford29, Heather C., Scheffer28, Ingrid E., Clayton-Smith53, Jill, Macaya45, Alfon, Rothman4, James E., Eichler 5, Evan E., Kullmann 4 &amp, Dimitri M., 1, Henry Houlden, Hanna1, SYNAPS Study Group Michael G., Bugiardini1, Enrico, Hostettler1, Isabel, O’Callaghan1, Benjamin, Khan1, Alaa, Cortese1, Andrea, O’Connor1, Emer, Yau1, Wai Y., Bourinaris1, Thoma, Kaiyrzhanov1, Rauan, Chelban1, Viorica, Madej1, Monika, Diana2, Maria C., Vari2, Maria S., Pedemonte2, Marina, Bruno2, Claudio, Balagura3, Ganna, Scala3, Marcello, Fiorillo3, Chiara, Nobili3, Lino, Malintan4, Nancy T., Zanetti4, Maria N., Krishnakumar4, Shyam S., Lignani4, Gabriele, Jepson4, James E. C., Broda43, Paolo, Baldassari43, Simona, Rossi43, Pia, Fruscione43, Floriana, Madia43, Francesca, Traverso43, Monica, De-Marco43, Patrizia, Pérez-Dueñas45, Belen, Munell45, Francina, Kriouile57, Yamna, El-Khorassani57, Mohamed, Karashova58, Blagovesta, Avdjieva58, Daniela, Kathom58, Hadil, Tincheva58, Radka, Van-Maldergem59, Lionel, Nachbauer60, Wolfgang, Boesch60, Sylvia, Gagliano61, Antonella, Amadori62, Elisabetta, Goraya63, Jatinder S., Sultan64, Tipu, Kirmani65, Salman, Ibrahim66, Shahnaz, Jan66, Farida, Mine67, Jun, Banu68, Selina, Veggiotti69, Pierangelo, Zuccotti69, Gian V., Ferrari70, Michel D., Van Den Maagdenberg70, Arn M. J., Verrotti71, Alberto, Marseglia72, Gian L., Savasta72, Salvatore, Soler73, Miguel A., Scuderi74, Carmela, Borgione74, Eugenia, Chimenz75, Roberto, Gitto75, Eloisa, Dipasquale75, Valeria, Sallemi75, Alessia, Fusco75, Monica, Cuppari75, Caterina, Cutrupi75, Maria C., Ruggieri76, Martino, Cama77, Armando, Capra77, Valeria, Mencacci78, Niccolò E., Boles79, Richard, Gupta80, Neerja, Kabra80, Madhulika, Papacostas81, Savva, Zamba-Papanicolaou81, Eleni, Dardiotis82, Efthymio, Maqbool83, Shazia, Rana84, Nuzhat, Atawneh85, Osama, Lim86, Shen Y., Shaikh87, Farooq, Koutsis88, George, Breza88, Marianthi, Coviello89, Domenico A., Dauvilliers90, Yves A., Alkhawaja91, Issam, Alkhawaja92, Mariam, Al-Mutairi93, Fuad, Stojkovic94, Tanya, Ferrucci, Veronica, Zollo, Massimo, Alkuraya96, Fowzan S., Kinali97, Maria, Sherifa98, Hamed, Benrhouma99, Hanene, Turki99, Ilhem B. Y., Tazir100, Meriem, Obeid101, Makram, Bakhtadze102, Sophia, Saadi103, Nebal W., Zaki104, Maha S., Triki105, Chahnez C., Benfenati106, Fabio, Gustincich106, Stefano, Kara107, Majdi, Belcastro108, Vincenzo, Specchio109, Nicola, Capovilla110, Giuseppe, Karimiani111, Ehsan G., Salih112, Ahmed M., Okubadejo113, Njideka U., Ojo113, Oluwadamilola O., Oshinaike113, Olajumoke O., Oguntunde113, Olapeju, Wahab114, Kolawole, Bello114, Abiodun H., Abubakar115, Sanni, Obiabo116, Yahaya, Nwazor117, Ernest, Ekenze118, Oluchi, Williams119, Uduak, Iyagba120, Alagoma, Taiwo121, Lolade, Komolafe122, Morenikeji, Senkevich123, Konstantin, Shashkin124, Chingiz, Zharkynbekova125, Nazira, Koneyev126, Kairgali, Manizha127, Ganieva, Isrofilov127, Maksud, Guliyeva128, Ulviyya, Salayev129, Kamran, Khachatryan130, Samson, Rossi131, Salvatore, Silvestri131, Gabriella, Haridy132, Nourelhoda, Ramenghi133, Luca A., Xiromerisiou134, Georgia, David135, Emanuele, Aguennouz136, Mhammed, Fidani137, Liana, Spanaki138 &amp, Cleanthe, and Tucci139, Arianna
Subjects: Male, [SDV.GEN] Life Sciences [q-bio]/Genetics, Ion channels in the nervous system, Cohort Studies, fluids and secretions, Loss of Function Mutation, Receptors, AMPA, AMPA receptor, lcsh:Science, Child, reproductive and urinary physiology, AMPA receptor, GluA2, neurodevelopmental disorders, autism spectrum disorder, glutamatergic synaptic transmission, GRIA2, neurodevelopmental disorders, Developmental disorders, Neurodevelopmental disorders, Brain, Magnetic Resonance Imaging, Settore MED/26 - NEUROLOGIA, GluA2, Child, Preschool, Female, Adult, Heterozygote, Adolescent, Science, autism spectrum disorder, Article, Young Adult, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Intellectual Disability/genetics, Neurodevelopmental Disorders/genetics, Receptors AMPA/genetics, Intellectual Disability, mental disorders, Humans, Infant, Neurodevelopmental Disorders, Receptors, AMPA, GRIA2, Preschool, Ion channel in the nervous system, Developmental disorders, Synaptic development, NG sequencing, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, glutamatergic synaptic transmission, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, NG sequencing, Synaptic development, Ion channel in the nervous system, Next-generation sequencing, lcsh:Q
Abstract: AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission., Genetic variants in ionotropic glutamate receptors have been implicated in neurodevelopmental disorders. Here, the authors report heterozygous de novo mutations in the GRIA2 gene in 28 individuals with intellectual disability and neurodevelopmental abnormalities associated with reduced Ca2+ transport and AMPAR currents.”
Published: 2019

287. De novo SCN1A mutations in migrating partial seizures of infancy

Author: Samuel F. Berkovic, David R. Thorburn, L. Hamiwka, Arvid Suls, Heather C Mefford, P. De Jonghe, Leanne M. Dibbens, B. Appleton, Todor Arsov, Mark T Mackay, Elaine C. Wirrell, Simone C. Yendle, Ingrid E. Scheffer, Tommy Stödberg, Thierry Bienvenu, Jeremy L. Freeman, Kent Kelley, Jacinta M McMahon, John C. Mulley, D. Carranza Rojo, Rojo, D Carranza, Hamiwka, L, McMahon, JM, Dibbens, LM, Arsov, T, Suls, A, Stodberg, T, Kelley, K, Wirrell, E, Appleton, B, Mackay, M, Freeman, JL, Yendle, SC, Berkovic, SF, Bienvenu, T, De Jonghe, P, Thorburn, DR, Mulley, JC, Mefford, HC, and Scheffer, IE
Subjects: Male, Pathology, medicine.medical_specialty, DNA Copy Number Variations, CDKL5, Nerve Tissue Proteins, DNA-Directed DNA Polymerase, Protein Serine-Threonine Kinases, Biology, Bioinformatics, Sodium Channels, Epilepsy, Munc18 Proteins, Dravet syndrome, Convulsion, medicine, Humans, STXBP1, Missense mutation, Genetic Predisposition to Disease, Genetic Testing, Copy-number variation, Child, Genetic testing, severe infantile multifocal epilepsy, medicine.diagnostic_test, copy number variation, Infant, Articles, Cadherins, medicine.disease, Protocadherins, DNA Polymerase gamma, NAV1.1 Voltage-Gated Sodium Channel, epileptic encephalopathy, Child, Preschool, Mutation, Female, Human medicine, Epilepsies, Partial, Neurology (clinical), medicine.symptom
Abstract: Objective: To determine the genetic etiology of the severe early infantile onset syndrome of malignant migrating partial seizures of infancy (MPSI). Methods: Fifteen unrelated children with MPSI were screened for mutations in genes associated with infantile epileptic encephalopathies: SCN1A, CDKL5, STXBP1, PCDH19, and POLG. Microarray studies were performed to identify copy number variations. Results: One patient had a de novo SCN1A missense mutation p.R862G that affects the voltage sensor segment of SCN1A. A second patient had a de novo 11.06 Mb deletion of chromosome 2q24.2q31.1 encompassing more than 40 genes that included SCN1A. Screening of CDKL5 (13/15 patients), STXBP1 (13/15), PCDH19 (9/11 females), and the 3 common European mutations of POLG (11/15) was negative. Pathogenic copy number variations were not detected in 11/12 cases. Conclusion: Epilepsies associated with SCN1A mutations range in severity from febrile seizures to severe epileptic encephalopathies including Dravet syndrome and severe infantile multifocal epilepsy. MPSI is now the most severe SCN1A phenotype described to date. While not a common cause of MPSI, SCN1A screening should now be considered in patients with this devastating epileptic encephalopathy. GLOSSARY: CNV: copy number variation EE: epileptic encephalopathy MPSI: malignant migrating partial seizures of infancy SIMFE: severe infantile multifocal epilepsy.
Published: 2011

288. Recurrence risk of epilepsy and mental retardation in females due to parental mosaicism of PCDH19 mutations

Author: Tejal A. Desai, John A. Damiano, Anne Ronan, Fiona Haslam McKenzie, Rachel Kneen, Marta A. Bayly, Sarah E. Heron, John C. Mulley, Leanne M. Dibbens, J. Gibbs, Ingrid E. Scheffer, Todor Arsov, Dibbens, LM, Kneen, R, Bayly, MA, Heron, SE, Arsov, T, Damiano, JA, Desai, T, Gibbs, J, McKenzie, F, Mulley, JC, Ronan, A, and Scheffer, IE
Subjects: Male, Parents, Adolescent, Genetic counseling, media_common.quotation_subject, DNA Mutational Analysis, Germline mosaicism, Sister, Polymorphism, Single Nucleotide, Young Adult, Epilepsy, Recurrence, single nucleotide polymorphism, Intellectual Disability, medicine, Humans, Missense mutation, media_common, Family Health, Genetics, Daughter, Mosaicism, Cadherins, medicine.disease, Protocadherins, Dravet syndrome, Developmental disorder, Mutation (genetic algorithm), epilepsy, Female, Neurology (clinical), Psychology
Abstract: Objective: Two unrelated families were ascertained in which sisters had infantile onset of epilepsy and developmental delay. Mutations in the protocadherin 19 ( PCDH19 ) gene cause epilepsy and mental retardation limited to females (EFMR). Despite both sister pairs having a PCDH19 mutation, neither parent in each family was a heterozygous carrier of the mutation. The possibility of parental mosaicism of PCDH19 mutations was investigated. Methods: Genomic DNA from peripheral blood was obtained and sequenced for PCDH19 mutations. Parentage was confirmed by markers. Results: Both sister pairs have a mutation in PCDH19 . Sister pair 1 has a missense mutation, c.74T>C, L25P, while sequence analysis indicates both of their parents are negative for the mutation. Diagnostic restriction enzyme analysis detected low-level mosaicism of the mutation in their mother. Sister pair 2 are half-sisters who share a mother and each has the missense PCDH19 mutation c.1019 A>G, N340S. The sequence chromatograph of their mother shows reduced signal for the same mutation. These data indicate maternal somatic and gonadal mosaicism of the PCDH19 mutation in both sister pairs. Phenotyping is suggestive of, and PCDH19 mutation detection is diagnostic for, the disorder EFMR in the affected girls. Conclusions: We show that gonadal mosaicism of a PCDH19 mutation in a parent is an important molecular mechanism associated with the inheritance of EFMR. This should be considered when providing genetic counseling for couples who have one affected daughter as they may risk recurrence of affected daughters and having sons at risk of transmitting EFMR.
Published: 2011

289. The role of neuronal GABAA receptor subunit mutations in idiopathic generalized epilepsies

Author: Alison L. Clarke, Michaella C. Richards, Samuel F. Berkovic, Leanne M. Dibbens, Bree L. Hodgson, Steve Petrou, Louise A. Harkin, Ingrid E. Scheffer, John C. Mulley, Dibbens, LM, Harkin, LA, Richards, M, Hodgson, BL, Clarke, AL, Petrou, S, Scheffer, IE, Berkovic, SF, and Mulley, JC
Subjects: Protein subunit, idiopathic generalized epilepsy, Biology, medicine.disease_cause, genetic epilepsy with febrile seizures plus, Idiopathic generalized epilepsy, Cohort Studies, Xenopus laevis, Childhood absence epilepsy, Channelopathy, Genetic variation, medicine, Animals, Humans, Psychology, febrile seizures, genetics, Gene, Neurons, Mutation, GABAA receptor, General Neuroscience, GABAA receptors, Neurosciences, Brain, Genetic Variation, medicine.disease, Receptors, GABA-A, Protein Subunits, nervous system, Oocytes, Epilepsy, Generalized, Female, Neuroscience
Abstract: Rare GABAA receptor γ2 and α1 subunit mutations of pathogenic effect have been described segregating in families with “monogenic” epilepsies. We now report globally on the genetic variation contained within all 16 neuronal GABAA receptor subunit genes from the one patient cohort. The cohort consists of GEFS+, FS, and IGE subgroups as either sporadic cases or index cases from small families, with one index case from one large IGE family. The rarity of mutations and coding variation in general across all of the subunits suggests a low tolerance for mutations affecting GABA mediated neuronal inhibition. Characterization of the broader channelopathy load associated with susceptibility to these common epilepsies mostly with complex genetics will need to be expanded beyond the family of GABAA receptor subunits to all families of neuronal ion channels and their interacting molecules by systematic mutation detection associated with functional investigation of their naturally occurring genetic variations. Refereed/Peer-reviewed
Published: 2009

290. Epileptic spasms are a feature ofDEPDC5mTORopathy

Author: Samuel F. Berkovic, Simone Mandelstam, Douglas E. Crompton, Matthew Zemel, Gemma L. Carvill, Amy L Schneider, Jacinta M McMahon, A. Simon Harvey, Julia Saykally, Joseph Sullivan, Brigid M. Regan, Saul A. Mullen, Katherine B. Howell, Leanne M. Dibbens, Heather C Mefford, Ingrid E. Scheffer, Richard J. Leventer, Carvill, GL, Crompton, DE, Regan, BM, McMahon, JM, Saykally, J, Zemel, M, Schneider, AL, Dibbens, L, Howell, KB, Mandelstam, S, Leventer, RJ, Harvey, AS, Mullen, SA, Berkovic, SF, Sullivan, J, Scheffer, IE, and Mefford, HC
Subjects: familial focal epilepsy, epileptic spasms, Bioinformatics, DEPDC5 mutations, Article, 03 medical and health sciences, Epilepsy, spasms, 0302 clinical medicine, medicine, Family history, Genetics (clinical), 030304 developmental biology, 0303 health sciences, business.industry, Cortical dysplasia, medicine.disease, NPRL3, DEPDC5, 3. Good health, Epileptic spasms, Clinical research, Cohort, epilepsy, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract: usc Refereed/Peer-reviewed Objective: To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. Methods: We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. Results: We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable. Conclusions: While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies.
Published: 2015

291. Eating habits and behaviors in children with Dravet syndrome: A case-control study.

Author: Laliberté A, Siafa L, Soufi A, Dassi C, Russ-Hall SJ, Scheffer IE, and Myers KA
Abstract: This study evaluated food preferences and eating behaviors of individuals with Dravet syndrome. Patients diagnosed with Dravet syndrome were recruited, as well as a control group composed of siblings of patients with epilepsy (any form). The Food Preference Questionnaire and the Child Eating Behavior Questionnaire were completed by caregivers along with two open-ended questions regarding eating challenges. Seventy-eight participants (45 with Dravet syndrome and 33 controls) were included. Compared to controls, mean scores for food preference were lower for fruits (p = .000099), meats and fish (p = .00094), and snacks (p = .000027) in Dravet syndrome. People with Dravet syndrome also had less emotional overeating (p = .0085) and food enjoyment (p = .0012), but more slowness in eating (p = .00021) and food fussiness (p = .0064). In a subgroup analysis of only pediatric (age <18 years) patients, similar results were observed for both food preferences and eating habits. In qualitative data, caregivers most commonly reported difficulties with fixation on specific foods. This study demonstrates specific food preferences and challenging eating behaviors in individuals with Dravet syndrome. These data provide potential avenues for nutritional interventions and behavioral therapies to increase the quality of life of patients and their families., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2024
Full Text: View/download PDF

292. Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).

Author: Viswanathan S, Oliver KL, Regan BM, Schneider AL, Myers CT, Mehaffey MG, LaCroix AJ, Antony J, Webster R, Cardamone M, Subramanian GM, Chiu ATG, Roza E, Teleanu RI, Malone S, Leventer RJ, Gill D, Berkovic SF, Hildebrand MS, Goad BS, Howell KB, Symonds JD, Brunklaus A, Sadleir LG, Zuberi SM, Mefford HC, and Scheffer IE
Subjects: Humans, Female, Male, Child, Preschool, Child, Infant, Adolescent, Electroencephalography, Sleep physiology, Sleep genetics, Cohort Studies, Phenotype, Adult, Young Adult, Spasms, Infantile genetics, Spasms, Infantile physiopathology
Abstract: Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS)., Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes., Results: We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: ATP1A2, CACNA1A, FOXP1, GRIN1, KCNMA1, KCNQ3, PPFIA3, PUF60, SETD1B, and ZBTB18, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS., Interpretation: DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024;96:932-943., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)
Published: 2024
Full Text: View/download PDF

293. Investigating the effect of polygenic background on epilepsy phenotype in 'monogenic' families.

Author: Oliver KL, Scheffer IE, Ellis CA, Grinton BE, Berkovic SF, and Bahlo M
Abstract: Background: Phenotypic variability within families with epilepsy is often observed, even when relatives share the same monogenic cause. We aimed to investigate whether common polygenic risk for epilepsy could explain the penetrance and phenotypic expression of rare pathogenic variants in familial epilepsies., Methods: We studied 58 clinically heterogeneous families with genetic epilepsy with febrile seizures plus (GEFS+). Relatives were coded as either unaffected or affected with epilepsy, and graded according to phenotype severity: no seizures, febrile seizures (FS) only, febrile seizures plus (FS+), generalised/focal epilepsy, or developmental and epileptic encephalopathy (DEE). Epilepsy polygenic risk scores (PRSs) were tested for association with epilepsy phenotype. Within families, the mean PRS difference was compared between pairs concordant versus discordant for phenotype severity. Statistical analyses were performed using mixed-effect regression models., Findings: 304 individuals segregating a known, or presumed, rare variant of large effect, were studied. Within families, higher epilepsy polygenic risk was associated with an epilepsy diagnosis (OR = 1.39, 95% CI 1.08, 1.80, p adj = 0.040). Relatives with a more severe phenotype had a mean pairwise PRS difference of +0.19 higher than relatives with a milder phenotype (p adj = 0.010). The difference increased with greater phenotype discordance between relatives. As the cohort included two rare variants with >30 relatives each, variant-specific genotype-phenotype associations could also be analysed. Whilst the epilepsy PRS effect was strong for relatives segregating the GABRG2 p.Arg82Gln pathogenic variant (p adj = 0.0010), the effect was not significant for SCN1B p.Cys121Trp., Interpretation: We provide support for genetic background modifying the penetrance and phenotypic expression of rare variants associated with 'monogenic' epilepsies. In GEFS+ families, relatives with higher epilepsy PRSs were more likely to show penetrance (epilepsy diagnosis) and a more severe phenotype. Variant-specific analyses suggest that some rare variants may be more susceptible to PRS modification, carrying important genetic counselling and disease prognostication implications for patients., Funding: National Health and Medical Research Council of Australia, Medical Research Future Fund of Australia., Competing Interests: Declaration of interests M.B. has received payment for thesis examination from University of Sydney, Australian National University, University of Melbourne; has received support for registration to the Genetics Society of AustralAsia and GeneMappers conferences; is/was a member of the Australian Academy of Health and Medical Sciences Reports Committee, the GenV Steering Committee, the Australian Academy of Health and Medical Sciences Australian Learned Academies Data Internetworking Network (ALADIN) Project Steering Committee, American Epilepsy Society Basic Sciences Committee, the Viertel Foundation Medical Advisory Board and a board member for the Australian Genome Research Facility. S.F.B has received educational grants from UCB Pharma, Eisai, SEER, Chiesi, LivaNova; consulting fees from Praxis Precision Medicines, Sequiris; speaker honoraria from Eisai, DeltaMed; serves as the Chief Medical Officer for the Epilepsy Foundation (Victoria); and has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies. I.E.S has served on scientific advisory boards for Bellberry Ltd, BioMarin, Chiesi, Eisai, Encoded Therapeutics, Garvan Institute of Medical Research, Knopp Biosciences, Longboard Pharmaceuticals, UCB, Takeda Pharmaceuticals; has received speaker honoraria from Akumentis Pharma, Biocodex, BioMarin, Chiesi, Eisai, GlaxoSmithKline, Liva Nova, Nutricia, Stoke Therapeutics, UCB, Zuellig Pharma; has received funding for travel from Biomarin, Eisai, GlaxoSmithKline, Stoke Therapeutics, UCB; has served as an investigator for Anavex Life Sciences, Cerebral Therapeutics, Cerecin Inc, Cereval Therapeutics, Eisai, Encoded Therapeutics, EpiMinder Inc, ES-Therapeutics, GW Pharmaceuticals, Marinus Pharmaceuticals, Neuren Pharmaceuticals, Neurocrine BioSciences, Ovid Therapeutics, Takeda Pharmaceuticals, UCB, Ultragenyx, Xenon Pharmaceuticals, Zogenix, Zynerba Pharmaceuticals; and has consulted for Biohaven Pharmaceuticals, Care Beyond Diagnosis, Cerecin Inc, Eisai, Epilepsy Consortium, Longboard Pharmaceuticals, UCB, Zynerba Pharmaceuticals; and is a Non-Executive Director of Bellberry Ltd and a Director of the Australian Academy of Health and Medical Sciences and the Australian Council of Learned Academies Ltd. She may accrue future revenue on pending patent WO2009/086591: Diagnostic And Therapeutic Methods For EFMR (Epilepsy And Mental Retardation Limited To Females); has a patent for SCN1A testing held by Bionomics Inc and licensed to various diagnostic companies; has a patent molecular diagnostic/theranostic target for benign familial infantile epilepsy (BFIE) [PRRT2] with royalties paid. C.A.E has received consulting fees from Epiminder Pty Ltd. The Epi4K Consortium was supported by an NINDS National Institute of Health Grant [U01NS077367]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Published: 2024
Full Text: View/download PDF

294. Early mortality in STXBP1-related disorders.

Author: Furia F, Rigby CS, Scheffer IE, Allen N, Baker K, Hengsbach C, Kegele J, Goss J, Gorman K, Mala MI, Nicita F, Allan T, Spalice A, Weber Y, Rubboli G, Møller RS, and Gardella E
Abstract: Introduction: Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders., Methods: Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease., Results: We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months-46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018)., Conclusion: We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies., (© 2024. The Author(s).)
Published: 2024
Full Text: View/download PDF

295. Practical considerations for the use of fenfluramine to manage patients with Dravet syndrome or Lennox-Gastaut syndrome in clinical practice.

Author: Wirrell EC, Lagae L, Scheffer IE, Cross JH, Specchio N, and Strzelczyk A
Subjects: Adolescent, Adult, Child, Child, Preschool, Humans, Young Adult, Selective Serotonin Reuptake Inhibitors therapeutic use, Selective Serotonin Reuptake Inhibitors adverse effects, Anticonvulsants therapeutic use, Anticonvulsants adverse effects, Epilepsies, Myoclonic drug therapy, Fenfluramine therapeutic use, Fenfluramine adverse effects, Lennox Gastaut Syndrome drug therapy
Abstract: Fenfluramine (FFA), an antiseizure medication (ASM) with serotonergic and sigma-1 receptor activity, is used to manage patients with developmental and epileptic encephalopathies (DEEs). It is approved in the US for treating seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS) in patients ≥2 years old and as add-on therapy for seizures associated with DS and LGS in the EU, UK, and Japan in similarly aged patients. Consensus guidelines for treatment of DS have recommended FFA to be an early-line ASM, and it has also shown efficacy in managing seizures associated with LGS. DS and LGS are DEEs associated with a range of seizure types, developmental impairments, and multiple comorbidities. Here we provide case vignettes describing 4 patients (3 DS and 1 LGS) aged 4-29 years old in whom up to 14 ASMs had previously failed, to illustrate real-world practice issues encountered by neurologists. This review provides guidance on the use of FFA in the context of ASM polytherapy and drug-drug interactions (DDIs), behavioral issues, dose titration, and adverse events. Along with data from the clinical trial program, these case vignettes emphasize the low risk of DDIs, a generally well-tolerated safety profile, and other seizure and nonseizure benefits (eg, improved cognition and sleep) associated with the use of FFA in DS or LGS. PLAIN LANGUAGE SUMMARY: Fenfluramine is used to treat seizures in individuals with Dravet syndrome and Lennox-Gastaut syndrome, but there are a range of issues that clinicians may face when treating patients. This review highlights four patients from the authors' everyday clinical work and offers guidance and practical considerations by neurologists with expertise in managing these complex conditions related to drug interactions, dosing, and side effects associated with fenfluramine., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2024
Full Text: View/download PDF

296. Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Author: Chen S, Abou-Khalil BW, Afawi Z, Ali QZ, Amadori E, Anderson A, Anderson J, Andrade DM, Annesi G, Arslan M, Auce P, Bahlo M, Baker MD, Balagura G, Balestrini S, Banks E, Barba C, Barboza K, Bartolomei F, Bass N, Baum LW, Baumgartner TH, Baykan B, Bebek N, Becker F, Bennett CA, Beydoun A, Bianchini C, Bisulli F, Blackwood D, Blatt I, Borggräfe I, Bosselmann C, Braatz V, Brand H, Brockmann K, Buono RJ, Busch RM, Caglayan SH, Canafoglia L, Canavati C, Castellotti B, Cavalleri GL, Cerrato F, Chassoux F, Cherian C, Cherny SS, Cheung CL, Chou IJ, Chung SK, Churchhouse C, Ciullo V, Clark PO, Cole AJ, Cosico M, Cossette P, Cotsapas C, Cusick C, Daly MJ, Davis LK, Jonghe P, Delanty N, Dennig D, Depondt C, Derambure P, Devinsky O, Di Vito L, Dickerson F, Dlugos DJ, Doccini V, Doherty CP, El-Naggar H, Ellis CA, Epstein L, Evans M, Faucon A, Feng YA, Ferguson L, Ferraro TN, Da Silva IF, Ferri L, Feucht M, Fields MC, Fitzgerald M, Fonferko-Shadrach B, Fortunato F, Franceschetti S, French JA, Freri E, Fu JM, Gabriel S, Gagliardi M, Gambardella A, Gauthier L, Giangregorio T, Gili T, Glauser TA, Goldberg E, Goldman A, Goldstein DB, Granata T, Grant R, Greenberg DA, Guerrini R, Gundogdu-Eken A, Gupta N, Haas K, Hakonarson H, Haryanyan G, Häusler M, Hegde M, Heinzen EL, Helbig I, Hengsbach C, Heyne H, Hirose S, Hirsch E, Ho CJ, Hoeper O, Howrigan DP, Hucks D, Hung PC, Iacomino M, Inoue Y, Inuzuka LM, Ishii A, Jehi L, Johnson MR, Johnstone M, Kälviäinen R, Kanaan M, Kara B, Kariuki SM, Kegele J, Kesim Y, Khoueiry-Zgheib N, Khoury J, King C, Klein KM, Kluger G, Knake S, Kok F, Korczyn AD, Korinthenberg R, Koupparis A, Kousiappa I, Krause R, Krenn M, Krestel H, Krey I, Kunz WS, Kurlemann G, Kuzniecky RI, Kwan P, La Vega-Talbott M, Labate A, Lacey A, Lal D, Laššuthová P, Lauxmann S, Lawthom C, Leech SL, Lehesjoki AE, Lemke JR, Lerche H, Lesca G, Leu C, Lewin N, Lewis-Smith D, Li GH, Liao C, Licchetta L, Lin CH, Lin KL, Linnankivi T, Lo W, Lowenstein DH, Lowther C, Lubbers L, Lui CHT, Macedo-Souza LI, Madeleyn R, Madia F, Magri S, Maillard L, Marcuse L, Marques P, Marson AG, Matthews AG, May P, Mayer T, McArdle W, McCarroll SM, McGoldrick P, McGraw CM, McIntosh A, McQuillan A, Meador KJ, Mei D, Michel V, Millichap JJ, Minardi R, Montomoli M, Mostacci B, Muccioli L, Muhle H, Müller-Schlüter K, Najm IM, Nasreddine W, Neaves S, Neubauer BA, Newton CRJC, Noebels JL, Northstone K, Novod S, O'Brien TJ, Owusu-Agyei S, Özkara Ç, Palotie A, Papacostas SS, Parrini E, Pato C, Pato M, Pendziwiat M, Pennell PB, Petrovski S, Pickrell WO, Pinsky R, Pinto D, Pippucci T, Piras F, Piras F, Poduri A, Pondrelli F, Posthuma D, Powell RHW, Privitera M, Rademacher A, Ragona F, Ramirez-Hamouz B, Rau S, Raynes HR, Rees MI, Regan BM, Reif A, Reinthaler E, Rheims S, Ring SM, Riva A, Rojas E, Rosenow F, Ryvlin P, Saarela A, Sadleir LG, Salman B, Salmon A, Salpietro V, Sammarra I, Scala M, Schachter S, Schaller A, Schankin CJ, Scheffer IE, Schneider N, Schubert-Bast S, Schulze-Bonhage A, Scudieri P, Sedláčková L, Shain C, Sham PC, Shiedley BR, Siena SA, Sills GJ, Sisodiya SM, Smoller JW, Solomonson M, Spalletta G, Sparks KR, Sperling MR, Stamberger H, Steinhoff BJ, Stephani U, Štěrbová K, Stewart WC, Stipa C, Striano P, Strzelczyk A, Surges R, Suzuki T, Talarico M, Talkowski ME, Taneja RS, Tanteles GA, Timonen O, Timpson NJ, Tinuper P, Todaro M, Topaloglu P, Tsai MH, Tumiene B, Turkdogan D, Uğur-İşeri S, Utkus A, Vaidiswaran P, Valton L, van Baalen A, Vari MS, Vetro A, Vlčková M, von Brauchitsch S, von Spiczak S, Wagner RG, Watts N, Weber YG, Weckhuysen S, Widdess-Walsh P, Wiebe S, Wolf SM, Wolff M, Wolking S, Wong I, von Wrede R, Wu D, Yamakawa K, Yapıcı Z, Yis U, Yolken R, Yücesan E, Zagaglia S, Zahnert F, Zara F, Zimprich F, Zizovic M, Zsurka G, Neale BM, and Berkovic SF
Abstract: Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies., Competing Interests: Competing Interests B.M.N is a member of the scientific advisory board at Deep Genomics and Neumora. No other authors have competing interests to declare
Published: 2024
Full Text: View/download PDF

297. Author Correction: Developmental and epileptic encephalopathies.

Author: Scheffer IE, Zuberi S, Mefford HC, Guerrini R, and McTague A
Published: 2024
Full Text: View/download PDF

298. Developmental and epileptic encephalopathies.

Author: Scheffer IE, Zuberi S, Mefford HC, Guerrini R, and McTague A
Subjects: Humans, Epilepsy diagnosis, Epilepsy genetics, Epilepsy therapy
Abstract: Developmental and epileptic encephalopathies, the most severe group of epilepsies, are characterized by seizures and frequent epileptiform activity associated with developmental slowing or regression. Onset typically occurs in infancy or childhood and includes many well-defined epilepsy syndromes. Patients have wide-ranging comorbidities including intellectual disability, psychiatric features, such as autism spectrum disorder and behavioural problems, movement and musculoskeletal disorders, gastrointestinal and sleep problems, together with an increased mortality rate. Problems change with age and patients require substantial support throughout life, placing a high psychosocial burden on parents, carers and the community. In many patients, the aetiology can be identified, and a genetic cause is found in >50% of patients using next-generation sequencing technologies. More than 900 genes have been identified as monogenic causes of developmental and epileptic encephalopathies and many cell components and processes have been implicated in their pathophysiology, including ion channels and transporters, synaptic proteins, cell signalling and metabolism and epigenetic regulation. Polygenic risk score analyses have shown that common variants also contribute to phenotypic variability. Holistic management, which encompasses antiseizure therapies and care for multimorbidities, is determined both by epilepsy syndrome and aetiology. Identification of the underlying aetiology enables the development of precision medicines to improve the long-term outcome of patients with these devastating diseases., (© 2024. Springer Nature Limited.)
Published: 2024
Full Text: View/download PDF

299. Inflation of polygenic risk scores caused by sample overlap and relatedness: Examples of a major risk of bias.

Author: Ellis CA, Oliver KL, Harris RV, Ottman R, Scheffer IE, Mefford HC, Epstein MP, Berkovic SF, and Bahlo M
Subjects: Humans, Cohort Studies, Polymorphism, Single Nucleotide, Female, Risk Factors, Genetic Risk Score, Multifactorial Inheritance genetics, Genome-Wide Association Study, Bias, Genetic Predisposition to Disease
Abstract: Polygenic risk scores (PRSs) are an important tool for understanding the role of common genetic variants in human disease. Standard best practices recommend that PRSs be analyzed in cohorts that are independent of the genome-wide association study (GWAS) used to derive the scores without sample overlap or relatedness between the two cohorts. However, identifying sample overlap and relatedness can be challenging in an era of GWASs performed by large biobanks and international research consortia. Although most genomics researchers are aware of best practices and theoretical concerns about sample overlap and relatedness between GWAS and PRS cohorts, the prevailing assumption is that the risk of bias is small for very large GWASs. Here, we present two real-world examples demonstrating that sample overlap and relatedness is not a minor or theoretical concern but an important potential source of bias in PRS studies. Using a recently developed statistical adjustment tool, we found that excluding overlapping and related samples was equal to or more powerful than adjusting for overlap bias. Our goal is to make genomics researchers aware of the magnitude of risk of bias from sample overlap and relatedness and to highlight the need for mitigation tools, including independent validation cohorts in PRS studies, continued development of statistical adjustment methods, and tools for researchers to test their cohorts for overlap and relatedness with GWAS cohorts without sharing individual-level data., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
Published: 2024
Full Text: View/download PDF

300. RNA variant assessment using transactivation and transdifferentiation.

Author: Nicolas-Martinez EC, Robinson O, Pflueger C, Gardner A, Corbett MA, Ritchie T, Kroes T, van Eyk CL, Scheffer IE, Hildebrand MS, Barnier JV, Rousseau V, Genevieve D, Haushalter V, Piton A, Denommé-Pichon AS, Bruel AL, Nambot S, Isidor B, Grigg J, Gonzalez T, Ghedia S, Marchant RG, Bournazos A, Wong WK, Webster RI, Evesson FJ, Jones KJ, Cooper ST, Lister R, Gecz J, and Jolly LA
Subjects: Humans, RNA genetics, RNA metabolism, CRISPR-Cas Systems, Cell Transdifferentiation genetics, Fibroblasts metabolism, Fibroblasts cytology, Transcriptional Activation, Neurons metabolism, Neurons cytology
Abstract: Understanding the impact of splicing and nonsense variants on RNA is crucial for the resolution of variant classification as well as their suitability for precision medicine interventions. This is primarily enabled through RNA studies involving transcriptomics followed by targeted assays using RNA isolated from clinically accessible tissues (CATs) such as blood or skin of affected individuals. Insufficient disease gene expression in CATs does however pose a major barrier to RNA based investigations, which we show is relevant to 1,436 Mendelian disease genes. We term these "silent" Mendelian genes (SMGs), the largest portion (36%) of which are associated with neurological disorders. We developed two approaches to induce SMG expression in human dermal fibroblasts (HDFs) to overcome this limitation, including CRISPR-activation-based gene transactivation and fibroblast-to-neuron transdifferentiation. Initial transactivation screens involving 40 SMGs stimulated our development of a highly multiplexed transactivation system culminating in the 6- to 90,000-fold induction of expression of 20/20 (100%) SMGs tested in HDFs. Transdifferentiation of HDFs directly to neurons led to expression of 193/516 (37.4%) of SMGs implicated in neurological disease. The magnitude and isoform diversity of SMG expression following either transactivation or transdifferentiation was comparable to clinically relevant tissues. We apply transdifferentiation and/or gene transactivation combined with short- and long-read RNA sequencing to investigate the impact that variants in USH2A, SCN1A, DMD, and PAK3 have on RNA using HDFs derived from affected individuals. Transactivation and transdifferentiation represent rapid, scalable functional genomic solutions to investigate variants impacting SMGs in the patient cell and genomic context., Competing Interests: Declaration of interests S.T.C. has no paid advisory roles to declare. S.T.C. is a volunteer member of ClinGen Expert Panels: Muscular Dystrophies and Myopathies GCEP and Limb Girdle Muscular Dystrophy VCEP. S.T.C. is named inventor of intellectual property (IP) relating to novel methods and biomarkers to identify DNA variants that alter pre-messenger RNA splicing: (1) PCT no. 2018904348 and (2) Australian Patent no. 2019379868. PCT no. 2019900836. This IP is unrelated to the data and outcomes described within this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2024
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Region

Database

Publisher

914 results on '"Scheffer, IE"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources