24 results on '"Rodriguez-Casero, V"'
Search Results
2. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination
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Ramanathan, Sudarshini, Mohammad, Shekeeb, Tantsis, Esther, Nguyen, Tina Kim, Merheb, Vera, Fung, Victor S C, White, Owen Bruce, Broadley, Simon, Lechner-Scott, Jeannette, Vucic, Steve, Henderson, Andrew P D, Barnett, Michael Harry, Reddel, Stephen W, Brilot, Fabienne, Dale, Russell C, Andrews, Pi, Barton, Jl, Burrow, Jnc, Butzkueven, H, Cairns, Ag, Calvert, S, Caruana, P, Chelakkadan, S, Clark, D, Fraser, Cl, Freeman, Jl, Gill, D, Grattan-smith, Pj, Gupta, S, Hardy, Ta, Kothur, K, Ling, Sr, Lopez, Ja, Malone, S, Marriott, Mp, Nosadini, M, O’grady, Gl, Orr, Cf, Ouvrier, R, Parratt, J, Patrick, E, Pilli, D, Riminton, Ds, Riney, K, Rodriguez-casero, V, Ryan, Mm, Scheffer, Ie, Shah, Uh, Shuey, N, Spooner, Cg, Subramanian, Gm, Tea, F, Thomas, T, Thompson, J, Troedson, C, Ware, Tl, Webster, Ri, Yiannikas, C, Yiu, Em, and Zou, A
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- 2018
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3. Unclassified white matter disorders: A diagnostic journey requiring close collaboration between clinical and laboratory services
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Stutterd, CA, Vanderver, A, Lockhart, PJ, Helman, G, Pope, K, Uebergang, E, Love, C, Delatycki, MB, Thorburn, D, Mackay, MT, Peters, H, Kornberg, AJ, Patel, C, Rodriguez-Casero, V, Waak, M, Silberstein, J, Sinclair, A, Nolan, M, Field, M, Davis, MR, Fahey, M, Scheffer, IE, Freeman, JL, Wolf, N, Taft, RJ, van der Knaap, MS, Simons, C, Leventer, RJ, Stutterd, CA, Vanderver, A, Lockhart, PJ, Helman, G, Pope, K, Uebergang, E, Love, C, Delatycki, MB, Thorburn, D, Mackay, MT, Peters, H, Kornberg, AJ, Patel, C, Rodriguez-Casero, V, Waak, M, Silberstein, J, Sinclair, A, Nolan, M, Field, M, Davis, MR, Fahey, M, Scheffer, IE, Freeman, JL, Wolf, N, Taft, RJ, van der Knaap, MS, Simons, C, and Leventer, RJ
- Abstract
BACKGROUND: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended. AIM: This study aimed to identify the genetic causes for a group of individuals with unclassified white matter disorders with suspected genetic aetiology and highlight the investigations required when the initial testing is non-diagnostic. METHODS: Twenty-six individuals from 22 families with unclassified white matter disorders underwent deep phenotyping and genome sequencing performed on trio, or larger, family groups. Functional studies and transcriptomics were used to resolve variants of uncertain significance with potential clinical relevance. RESULTS: Causative or candidate variants were identified in 15/22 (68.2%) families. Six of the 15 implicated genes had been previously associated with white matter disease (COL4A1, NDUFV1, SLC17A5, TUBB4A, BOLA3, DARS2). Patients with variants in the latter two presented with an atypical phenotype. The other nine genes had not been specifically associated with white matter disease at the time of diagnosis and included genes associated with monogenic syndromes, developmental disorders, and developmental and epileptic encephalopathies (STAG2, LSS, FIG4, GLS, PMPCA, SPTBN1, AGO2, SCN2A, SCN8A). Consequently, only 46% of the diagnoses would have been made via a current leukodystrophy gene panel test. DISCUSSION: These results confirm the importance of broad genomic testing for patients with white matter disorders. The high diagnostic yield reflects the integration of deep phenotyping, whole genome sequencing, trio analysis, functional studies, and transcriptomic analyses. CONC
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- 2022
4. The severe epilepsy syndromes of infancy: A population-based study.
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Dabscheck G., McMahon J.M., Mefford H.C., Panetta J., Riseley J., Rodriguez-Casero V., Ryan M.M., Schneider A.L., Smith L.J., Stark Z., Wong F., Yiu E.M., Scheffer I.E., Harvey A.S., Howell K.B., Freeman J.L., Mackay M.T., Fahey M.C., Archer J., Berkovic S.F., Chan E., Eggers S., Hayman M., Holberton J., Hunt R.W., Jacobs S.E., Kornberg A.J., Leventer R.J., Mandelstam S., Dabscheck G., McMahon J.M., Mefford H.C., Panetta J., Riseley J., Rodriguez-Casero V., Ryan M.M., Schneider A.L., Smith L.J., Stark Z., Wong F., Yiu E.M., Scheffer I.E., Harvey A.S., Howell K.B., Freeman J.L., Mackay M.T., Fahey M.C., Archer J., Berkovic S.F., Chan E., Eggers S., Hayman M., Holberton J., Hunt R.W., Jacobs S.E., Kornberg A.J., Leventer R.J., and Mandelstam S.
- Abstract
Objective: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. Method(s): A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. Result(s): Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. Significance: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, i
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- 2021
5. The severe epilepsy syndromes of infancy: A population-based study
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Howell, KB, Freeman, JL, Mackay, MT, Fahey, MC, Archer, J, Berkovic, SF, Chan, E, Dabscheck, G, Eggers, S, Hayman, M, Holberton, J, Hunt, RW, Jacobs, SE, Kornberg, AJ, Leventer, RJ, Mandelstam, S, McMahon, JM, Mefford, HC, Panetta, J, Riseley, J, Rodriguez-Casero, V, Ryan, MM, Schneider, AL, Smith, LJ, Stark, Z, Wong, F, Yiu, EM, Scheffer, IE, Harvey, AS, Howell, KB, Freeman, JL, Mackay, MT, Fahey, MC, Archer, J, Berkovic, SF, Chan, E, Dabscheck, G, Eggers, S, Hayman, M, Holberton, J, Hunt, RW, Jacobs, SE, Kornberg, AJ, Leventer, RJ, Mandelstam, S, McMahon, JM, Mefford, HC, Panetta, J, Riseley, J, Rodriguez-Casero, V, Ryan, MM, Schneider, AL, Smith, LJ, Stark, Z, Wong, F, Yiu, EM, Scheffer, IE, and Harvey, AS
- Abstract
OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initi
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- 2021
6. Neuronal Ceroid Lipofuscinosis type 2: an Australian case series
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Johnson, AM, Mandelstam, S, Andrews, I, Boysen, K, Yaplito-Lee, J, Fietz, M, Nagarajan, L, Rodriguez-Casero, V, Ryan, MM, Smith, N, Scheffer, IE, Ellaway, C, Johnson, AM, Mandelstam, S, Andrews, I, Boysen, K, Yaplito-Lee, J, Fietz, M, Nagarajan, L, Rodriguez-Casero, V, Ryan, MM, Smith, N, Scheffer, IE, and Ellaway, C
- Abstract
AIM: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative disorder presenting in children aged 2-4 years with seizures and loss of motor and language skills, followed by blindness and death in late childhood. Initial presenting features are similar to a range of common epilepsies. We aim to highlight typical clinical and radiological features that may prompt diagnosis of CLN2 disease in early disease stages. METHODS: We present a series of 13 Australian patients with CLN2 disease, describing clinical features, disease evolution, neuroimaging, electroencephalogram, biochemical and genetic results. Expert neuroradiological magnetic resonance imaging (MRI) analysis was retrospectively performed on 10 cases. RESULTS: Twelve patients presented with seizures, with initial seizures being focal (n = 4), generalised tonic-clonic (n = 3), absence (n = 3) and febrile (n = 2). Eleven patients (85%) had a language delay before the onset of seizures. Cerebellar or cerebral atrophy was noted in all patients on centralised MRI review, with abnormalities of the brain-stem, ventricles, corpus callosum and hippocampi. CONCLUSIONS: Early language delay with the onset of seizures at 2-4 years of age is the hallmark of CLN2 disease. MRI findings of early subtle atrophy in the cerebellum or posterior cortical regions should hasten testing for CLN2 disease to enable early initiation of enzyme replacement therapy.
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- 2020
7. Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination
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Ramanathan, S, Mohammad, S, Tantsis, E, Nguyen, Tk, Merheb, V, Fung, Vsc, White, Ob, Broadley, S, Lechner-Scott, J, Vucic, S, Henderson, Apd, Barnett, Mh, Reddel, Sw, Brilot, F, Dale, Rc, Australasian and New Zealand MOG Study Group Andrews, P, Barton, J, Burrow, J, Butzkueven, H, Cairns, A, Calvert, S, Caruana, P, Chelakkadan, S, Clark, D, Fraser, C, Freeman, J, Gill, D, Grattan-Smith, P, Gupta, S, Hardy, T, Kothur, K, Ling, S, Lopez, J, Malone, S, Marriott, M, Nosadini, M, O'Grady, G, Orr, C, Ouvrier, R, Parratt, J, Patrick, E, Pilli, D, Riminton, D, Riney, K, Rodriguez-Casero, V, Ryan, M, Scheffer, I, Shah, U, Shuey, N, Spooner, C, Subramanian, G, Tea, F, Thomas, T, Thompson, J, Troedson, C, Ware, T, Webster, R, Yiannikas, C, Yiu, E, and Zou, A.
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Male ,0301 basic medicine ,Journal Club ,medicine.medical_treatment ,Demyelinating Autoimmune Diseases, CNS ,Cohort Studies ,0302 clinical medicine ,Prednisone ,Child ,10. No inequality ,MOG antibody, demyelination, treatment ,treatment ,biology ,Encephalomyelitis, Acute Disseminated ,Neuromyelitis Optica ,Brain ,Immunoglobulins, Intravenous ,Middle Aged ,Magnetic Resonance Imaging ,3. Good health ,Psychiatry and Mental health ,Child, Preschool ,Acute disseminated encephalomyelitis ,Cohort ,Female ,demyelination ,Immunotherapy ,Antibody ,Rituximab ,Immunosuppressive Agents ,medicine.drug ,MOG antibody ,Adult ,medicine.medical_specialty ,Optic Neuritis ,Adolescent ,Myelitis, Transverse ,Myelin oligodendrocyte glycoprotein ,Young Adult ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Immunologic Factors ,Optic neuritis ,Aged ,Autoantibodies ,Expanded Disability Status Scale ,business.industry ,Infant ,Mycophenolic Acid ,medicine.disease ,030104 developmental biology ,Immunology ,biology.protein ,Myelin-Oligodendrocyte Glycoprotein ,Surgery ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
ObjectiveWe characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination.MethodsWe evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients.ResultsThe most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses ConclusionRelapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation.
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- 2017
8. Cerebral hypomyelination associated with biallelic variants of FIG4
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Lenk, GM, Berry, IR, Stutterd, CA, Blyth, M, Green, L, Vadlamani, G, Warren, D, Craven, I, Fanjul-Fernandez, M, Rodriguez-Casero, V, Lockhart, PJ, Vanderver, A, Simons, C, Gibb, S, Sadedin, S, White, SM, Christodoulou, J, Skibina, O, Ruddle, J, Tan, TY, Leventer, RJ, Livingston, JH, Meisler, MH, Lenk, GM, Berry, IR, Stutterd, CA, Blyth, M, Green, L, Vadlamani, G, Warren, D, Craven, I, Fanjul-Fernandez, M, Rodriguez-Casero, V, Lockhart, PJ, Vanderver, A, Simons, C, Gibb, S, Sadedin, S, White, SM, Christodoulou, J, Skibina, O, Ruddle, J, Tan, TY, Leventer, RJ, Livingston, JH, and Meisler, MH
- Abstract
The lipid phosphatase gene FIG4 is responsible for Yunis-Varón syndrome and Charcot-Marie-Tooth disease Type 4J, a peripheral neuropathy. We now describe four families with FIG4 variants and prominent abnormalities of central nervous system (CNS) white matter (leukoencephalopathy), with onset in early childhood, ranging from severe hypomyelination to mild undermyelination, in addition to peripheral neuropathy. Affected individuals inherited biallelic FIG4 variants from heterozygous parents. Cultured fibroblasts exhibit enlarged vacuoles characteristic of FIG4 dysfunction. Two unrelated families segregate the same G > A variant in the +1 position of intron 21 in the homozygous state in one family and compound heterozygous in the other. This mutation in the splice donor site of exon 21 results in read-through from exon 20 into intron 20 and truncation of the final 115 C-terminal amino acids of FIG4, with retention of partial function. The observed CNS white matter disorder in these families is consistent with the myelination defects in the FIG4 null mouse and the known role of FIG4 in oligodendrocyte maturation. The families described here the expanded clinical spectrum of FIG4 deficiency to include leukoencephalopathy.
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- 2019
9. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
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Mefford H.C., Andrade D.M., Freeman J.L., Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J., Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G., Stanley T., Bye A.M.E., Bleasel A., Howell K.B., Kivity S., Mackay M.T., Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N., Lerman-Sagie T., Lev D., Moller R.S., Gill D., Mefford H.C., Andrade D.M., Freeman J.L., Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J., Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G., Stanley T., Bye A.M.E., Bleasel A., Howell K.B., Kivity S., Mackay M.T., Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N., Lerman-Sagie T., Lev D., Moller R.S., and Gill D.
- Abstract
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders. © 2013 Nature America, Inc. All rights reserved.
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- 2013
10. Targeted resequencing in epileptic encephalopathies reveals marked genetic heterogeneity and novel genes.
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Scheffer I.E., Shendure J., Berkovic S.F., Mefford H.C., Carvill G.L., Heavin S.B., Yendle S.C., O'Roak B.J., Cook J., Khan A., Dorschner M.O., Weaver M.A., Calvert S., Malone S., Wallace G., Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T., Rodriguez-Casero V., Webster R., Korczyn A., Zelnick N., Lerman-Sagie T., Lev D., SteensbjerreMoller R., Andrade D.M., Freeman J.L., Sadleir L.G., Scheffer I.E., Shendure J., Berkovic S.F., Mefford H.C., Carvill G.L., Heavin S.B., Yendle S.C., O'Roak B.J., Cook J., Khan A., Dorschner M.O., Weaver M.A., Calvert S., Malone S., Wallace G., Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T., Rodriguez-Casero V., Webster R., Korczyn A., Zelnick N., Lerman-Sagie T., Lev D., SteensbjerreMoller R., Andrade D.M., Freeman J.L., and Sadleir L.G.
- Abstract
Purpose: Epileptic encephalopathies (EEs) are a devastating group of epilepsies characterized by refractory seizures, cognitive arrest or regression, associated with ongoing epileptic activity, and a poor prognosis. De novo mutations in a number of genes, as well as rare, de novo copy number changes, are known to cause EE. However, the vast majority of cases have an unknown etiology. Method(s): We performed targeted massively parallel resequencing of 18 known and 47 candidate EE genes in 500 patients to identify novel genes, and investigate the phenotypic spectrum of known genes. Result(s): Overall, we identify pathogenic mutations in 10% of our cohort. Pathogenic variants were found in seven of our 47 candidate genes, collectively accounting for 3% of EE in our cohort. Most notably, we identify mutations in 1.2% of our cohort in a novel gene that acts in the chromatin remodeling pathway. Also, de novo mutations were detected in 1% of the cohort in SYNGAP1, a gene identified in individuals with intellectual disability. The remaining pathogenic variants were detected in known EE genes. For some, including SCN1A, SCN2A, and SCN8A, we expand the phenotypic spectrum, presenting novel clinical features associated with these genes. Conclusion(s): We have developed a rapid, cost-effective ($1/gene/proband) and efficient targeted resequencing approach to define the molecular etiology of EE. These results will transform molecular diagnostic approaches and facilitate the management of families affected by this devastating disorder. Furthermore, we have identified the chromatin remodeling pathway as a novel biological process involved in epileptogenesis. Future studies of this pathway will provide new avenues for development of therapeutic interventions.
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- 2013
11. International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines
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Dodd, C.N. (Caitlin), Romio, S.A. (Silvana), Black, S. (Steve), Vellozzi, C. (Claudia), Andrews, N.J. (Nick), Sturkenboom, M.C.J.M. (Miriam), Zuber, P. (Patrick), Hua, W. (Wei), Bonhoeffer, J. (Jan), Buttery, J. (Jim), Crawford, N. (Nigel), Deceuninck, G. (Genevieve), Vries, C.S. (Corinne) de, Wals, P. (Philippe) de, Gimeno, D. (David), Heijbel, H. (Harald), Hughes, H. (Hayley), Hur, K. (Kwan), Hviid, A. (Anders), Kelman, J. (Jeffrey), Kilpi, T. (Tehri), Chuang, S.K. (S.), Macartney, T. (Thomas), Rett, M. (Melisa), Lopez-Callada, V.R. (Vesta Richardson), Salmon, D. (Daniel), Sanchez, F.G. (Francisco Gimenez), Sanz, N. (Nuria), Silverman, B. (Bernard), Storsaeter, J. (Jann), Thirugnanam, U. (Umapathi), Maas, N.A.T. (Nicoline) van der, Yih, K. (Katherine), Zhang, T. (Teng Fei), Izurieta, H.S. (Hector), Addis, B.J., Akhtar, A. (Aysha), Cope, J. (Judith), Davis, R.L. (Robert), Gargiullo, P. (Paul), Kurz, X. (Xavier), Law, B. (Barbara), Sahinovic, I. (Isabelle), Tokars, J. (Jerry), Serrano, P. (Pedro), Cheng, A. (Aixin), Charles, P. (Pat), Clothier, H. (Hazel), Day, B. (Bruce), Day, T. (Timothy), Gates, P. (Peter), MacDonnell, R. (Richard), Roberts, L. (Les), Rodriguez-Casero, V. (Vic-toria), Wijeratne, T. (Tissa), Kiers, H.A.L. (Henk), Blyth, C. (Christopher), Booy, R. (Robert), Elliott, E. (Elizabeth), Gold, M.R. (Michael), Marshall, H., McIntyre, P. (Peter), Richmond, P. (Peter), Royle, J. (Jenny), Wood, N.W. (Nicholas), Zurynski, Y. (Yvonne), Calvo, G. (Gonzalo), Campins, M. (Magda), Corominas, N. (Nuria), Torres, F. (Ferran), Valls, V., Vilella, A. (Ángels), Dutra, A. (Amalia), Eick-Cost, A. (Angelia), Jackson, H.M. (Henry), Garman, K. (Katherine), Hu, Z. (Zheng), Rigo, J., Badoo, J. (Judith), Cho, D (David), Polakowski, L.L. (Laura), Sandhu, S.K. (Sukhminder), Sun, G. (Guoying), Chan, H.-S.S. (Hoi-Shan Sophelia), Chan, K.-Y. (Kwok-Yin), Cheung, R. (Raymond), Cheung, Y-F. (Yuk-Fai), Cherk, S. (Sharon), Chuang, S.K (S.), Fok, D. (Dennis), Fung, B.-H. (Bun-Hey), Ko, K.-F. (Kwai-Fu), Lau, K.W. (Ka Wing), Lau, K.-K. (Kwok-Kwong), Li, P. (Pulin), Liu, H.-T. (Hui-Tung), Liu, S.-H. (Shao-Haei), Mok, K. (Kin), So, J. (Joanna), Wong, W. (Winnie), Wu, S.-P. (Shun-Ping), Ball, R. (Robert), Burwen, D. (Dale), Franks, R.L. (Riley), Gibbs, J.M. (Jonathan), Kliman, R.E. (Rebecca), Kropp, S. (Silke), MaCurdy, T.E. (Thomas), Martin, D.B. (David), Sandhu, S.-D.K. (Sukhmin-Der), Worrall, B.B. (Bradford B.), Fuentes, D.E.F. (Dra. Elvira Fuentes), González, P.C.O. (Paola Carolina Ojeda), Reyna, V.F. (Valerie ), Kulldorff, M. (Martin), Lee, G. (Grace), Lieu, T.A. (Tracy), Platt, S., Serres, G.D. (Gaston De), Jabin, K. (Kamilah), Soh, B.L.S. (Bee Leng Sally), Arnheim-Dahlström, L. (Lisen), Castot, A. (Anne), Melker, H.E. (Hester) de, Dieleman, J.P. (Jeanne), Hallgren, J. (Jonal), Jacobs, B.C. (Bart), Johansen, K. (Kari), Kramarz, P (Piotr), Lapeyre, M. (Maryse), Leino, T. (Tuija), Mølgaard-Nielsen, D. (Ditte), Mosseveld, M. (Mees), Olberg, H.K. (Henning K), Sammon, C.-M. (Cor-Mac), Saussier, C. (Christel), Schuemie, M.J. (Martijn), Sommet, A. (Agnès), Sparen, P. (Pär), Svanström, H. (Henrik), Vanrolleghem, A.M. (Ann M.), Weibel, D.M. (Daniel), Domingo, J.D. (Javier Diez), Esparza, J.L. (José LuísMicó), Lucas, R.M.O. (Rafael M. Ortí), Maseres, J.B.M. (Juan B. Mollar), Sánchez, J.L.A. (José Luís Alfonso), Sánchez, M.G. (Mercedes Garcés), Viguer, V.Z. (Vicente Zanón), Cunningham, F. (Francesca), Avagyan, A. (Armen), Thakkar, B. (Bharat), Zhang, R. (Rongping), Dodd, C.N. (Caitlin), Romio, S.A. (Silvana), Black, S. (Steve), Vellozzi, C. (Claudia), Andrews, N.J. (Nick), Sturkenboom, M.C.J.M. (Miriam), Zuber, P. (Patrick), Hua, W. (Wei), Bonhoeffer, J. (Jan), Buttery, J. (Jim), Crawford, N. (Nigel), Deceuninck, G. (Genevieve), Vries, C.S. (Corinne) de, Wals, P. (Philippe) de, Gimeno, D. (David), Heijbel, H. (Harald), Hughes, H. (Hayley), Hur, K. (Kwan), Hviid, A. (Anders), Kelman, J. (Jeffrey), Kilpi, T. (Tehri), Chuang, S.K. (S.), Macartney, T. (Thomas), Rett, M. (Melisa), Lopez-Callada, V.R. (Vesta Richardson), Salmon, D. (Daniel), Sanchez, F.G. (Francisco Gimenez), Sanz, N. (Nuria), Silverman, B. (Bernard), Storsaeter, J. (Jann), Thirugnanam, U. (Umapathi), Maas, N.A.T. (Nicoline) van der, Yih, K. (Katherine), Zhang, T. (Teng Fei), Izurieta, H.S. (Hector), Addis, B.J., Akhtar, A. (Aysha), Cope, J. (Judith), Davis, R.L. (Robert), Gargiullo, P. (Paul), Kurz, X. (Xavier), Law, B. (Barbara), Sahinovic, I. (Isabelle), Tokars, J. (Jerry), Serrano, P. (Pedro), Cheng, A. (Aixin), Charles, P. (Pat), Clothier, H. (Hazel), Day, B. (Bruce), Day, T. (Timothy), Gates, P. (Peter), MacDonnell, R. (Richard), Roberts, L. (Les), Rodriguez-Casero, V. (Vic-toria), Wijeratne, T. (Tissa), Kiers, H.A.L. (Henk), Blyth, C. (Christopher), Booy, R. (Robert), Elliott, E. (Elizabeth), Gold, M.R. (Michael), Marshall, H., McIntyre, P. (Peter), Richmond, P. (Peter), Royle, J. (Jenny), Wood, N.W. (Nicholas), Zurynski, Y. (Yvonne), Calvo, G. (Gonzalo), Campins, M. (Magda), Corominas, N. (Nuria), Torres, F. (Ferran), Valls, V., Vilella, A. (Ángels), Dutra, A. (Amalia), Eick-Cost, A. (Angelia), Jackson, H.M. (Henry), Garman, K. (Katherine), Hu, Z. (Zheng), Rigo, J., Badoo, J. (Judith), Cho, D (David), Polakowski, L.L. (Laura), Sandhu, S.K. (Sukhminder), Sun, G. (Guoying), Chan, H.-S.S. (Hoi-Shan Sophelia), Chan, K.-Y. (Kwok-Yin), Cheung, R. (Raymond), Cheung, Y-F. (Yuk-Fai), Cherk, S. (Sharon), Chuang, S.K (S.), Fok, D. (Dennis), Fung, B.-H. (Bun-Hey), Ko, K.-F. (Kwai-Fu), Lau, K.W. (Ka Wing), Lau, K.-K. (Kwok-Kwong), Li, P. (Pulin), Liu, H.-T. (Hui-Tung), Liu, S.-H. (Shao-Haei), Mok, K. (Kin), So, J. (Joanna), Wong, W. (Winnie), Wu, S.-P. (Shun-Ping), Ball, R. (Robert), Burwen, D. (Dale), Franks, R.L. (Riley), Gibbs, J.M. (Jonathan), Kliman, R.E. (Rebecca), Kropp, S. (Silke), MaCurdy, T.E. (Thomas), Martin, D.B. (David), Sandhu, S.-D.K. (Sukhmin-Der), Worrall, B.B. (Bradford B.), Fuentes, D.E.F. (Dra. Elvira Fuentes), González, P.C.O. (Paola Carolina Ojeda), Reyna, V.F. (Valerie ), Kulldorff, M. (Martin), Lee, G. (Grace), Lieu, T.A. (Tracy), Platt, S., Serres, G.D. (Gaston De), Jabin, K. (Kamilah), Soh, B.L.S. (Bee Leng Sally), Arnheim-Dahlström, L. (Lisen), Castot, A. (Anne), Melker, H.E. (Hester) de, Dieleman, J.P. (Jeanne), Hallgren, J. (Jonal), Jacobs, B.C. (Bart), Johansen, K. (Kari), Kramarz, P (Piotr), Lapeyre, M. (Maryse), Leino, T. (Tuija), Mølgaard-Nielsen, D. (Ditte), Mosseveld, M. (Mees), Olberg, H.K. (Henning K), Sammon, C.-M. (Cor-Mac), Saussier, C. (Christel), Schuemie, M.J. (Martijn), Sommet, A. (Agnès), Sparen, P. (Pär), Svanström, H. (Henrik), Vanrolleghem, A.M. (Ann M.), Weibel, D.M. (Daniel), Domingo, J.D. (Javier Diez), Esparza, J.L. (José LuísMicó), Lucas, R.M.O. (Rafael M. Ortí), Maseres, J.B.M. (Juan B. Mollar), Sánchez, J.L.A. (José Luís Alfonso), Sánchez, M.G. (Mercedes Garcés), Viguer, V.Z. (Vicente Zanón), Cunningham, F. (Francesca), Avagyan, A. (Armen), Thakkar, B. (Bharat), and Zhang, R. (Rongping)
- Abstract
Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination. Methods: The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach. Results: We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1
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- 2013
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12. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
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Carvill, GL, Heavin, SB, Yendle, SC, McMahon, JM, O'Roak, BJ, Cook, J, Khan, A, Dorschner, MO, Weaver, M, Calvert, S, Malone, S, Wallace, G, Stanley, T, Bye, AME, Bleasel, A, Howell, KB, Kivity, S, Mackay, MT, Rodriguez-Casero, V, Webster, R, Korczyn, A, Afawi, Z, Zelnick, N, Lerman-Sagie, T, Lev, D, Moller, RS, Gill, D, Andrade, DM, Freeman, JL, Sadleir, LG, Shendure, J, Berkovic, SF, Scheffer, IE, Mefford, HC, Carvill, GL, Heavin, SB, Yendle, SC, McMahon, JM, O'Roak, BJ, Cook, J, Khan, A, Dorschner, MO, Weaver, M, Calvert, S, Malone, S, Wallace, G, Stanley, T, Bye, AME, Bleasel, A, Howell, KB, Kivity, S, Mackay, MT, Rodriguez-Casero, V, Webster, R, Korczyn, A, Afawi, Z, Zelnick, N, Lerman-Sagie, T, Lev, D, Moller, RS, Gill, D, Andrade, DM, Freeman, JL, Sadleir, LG, Shendure, J, Berkovic, SF, Scheffer, IE, and Mefford, HC
- Abstract
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.
- Published
- 2013
13. 8. Neurophysiologic findings in children presenting with pes cavus
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Mohamed, A., primary, Watson, S.J., additional, Kornberg, A.J., additional, Rodriguez-Casero, V., additional, and Ryan, M.M., additional
- Published
- 2010
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14. Sodium channel 1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms
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Wallace, R. H., primary, Hodgson, B. L., additional, Grinton, B. E., additional, Gardiner, R. M., additional, Robinson, R., additional, Rodriguez-Casero, V., additional, Sadleir, L., additional, Morgan, J., additional, Harkin, L. A., additional, Dibbens, L. M., additional, Yamamoto, T., additional, Andermann, E., additional, Mulley, J. C., additional, Berkovic, S. F., additional, and Scheffer, I. E., additional
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- 2003
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15. Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms.
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Wallace, R H, Hodgson, B L, Grinton, B E, Gardiner, R M, Robinson, R, Rodriguez-Casero, V, Sadleir, L, Morgan, J, Harkin, L A, Dibbens, L M, Yamamoto, T, Andermann, E, Mulley, J C, Berkovic, S F, and Scheffer, I E
- Published
- 2003
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16. Anti-voltage-Gated Potassium Channel (VGKC) Antibodies and Acquired Neuromyotonia in Patients with Immune Dysregulation, Polyendocrinopathy, Enteropathy X-Lined (IPEX) Syndrome.
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Moseley N, King J, Van Dort B, Williams S, Rodriguez-Casero V, Ramachandran S, Choo S, Cole T, and McLean-Tooke A
- Subjects
- Adolescent, Child, Diabetes Mellitus, Type 1 blood, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 immunology, Diabetes Mellitus, Type 1 therapy, Diarrhea genetics, Diarrhea immunology, Diarrhea therapy, Forkhead Transcription Factors genetics, Genetic Diseases, X-Linked genetics, Genetic Diseases, X-Linked immunology, Genetic Diseases, X-Linked therapy, Hematopoietic Stem Cell Transplantation, Humans, Immune System Diseases blood, Immune System Diseases genetics, Immune System Diseases immunology, Immune System Diseases therapy, Infant, Newborn, Isaacs Syndrome genetics, Isaacs Syndrome immunology, Isaacs Syndrome therapy, Male, Mutation, Autoantibodies blood, Diabetes Mellitus, Type 1 congenital, Diarrhea blood, Genetic Diseases, X-Linked blood, Immune System Diseases congenital, Isaacs Syndrome blood, Potassium Channels, Voltage-Gated immunology
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- 2021
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17. Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder.
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Helman G, Taylor LE, Walkiewicz M, Le Moing M, Eggers S, Yaplito-Lee J, Fuller M, Dabscheck G, Rodriguez-Casero V, White SM, and Simons C
- Subjects
- Aminopeptidases metabolism, Cells, Cultured, Child, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases metabolism, Female, Humans, Neuronal Ceroid-Lipofuscinoses pathology, Serine Proteases metabolism, Tripeptidyl-Peptidase 1, Aminopeptidases genetics, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases genetics, Mutation, Neuronal Ceroid-Lipofuscinoses genetics, RNA Splicing, Serine Proteases genetics
- Abstract
RNA sequencing (RNAseq) is emerging as a complementary tool to DNA sequencing, providing utility in diagnosis for disorders such as neuronal ceroid lipofuscinosis CLN2 disease. We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.4:c.225A>G; p.(Gln75 = ) and NM_000391.4:c.1012C>G; p.(Gln338Glu), both classified as variants of uncertain significance. TPP1 activity was found to be significantly reduced in fibroblasts of the affected individual. RNAseq was performed to assess the impact of compound heterozygous variants in TPP1 and enabled the identification of three aberrant splicing events. The c.225A>G variant introduces a 5 nucleotide truncation of exon 3 and a loss of reading frame. The majority of CLN2 transcripts exclude either exon 8 or exons 7-8, resulting in large in-frame deletions. Isoform specific RT-PCR confirmed the aberrant splicing events are mutually exclusive, suggesting that the paternal exon 8 c.1012C>G variant results in exon skipping. This case study demonstrates how RNAseq can be used as an orthogonal test to inform the interpretation of some variants of unknown significance and its particular importance in disorders where effective disease management requires early diagnosis., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)
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- 2021
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18. The severe epilepsy syndromes of infancy: A population-based study.
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Howell KB, Freeman JL, Mackay MT, Fahey MC, Archer J, Berkovic SF, Chan E, Dabscheck G, Eggers S, Hayman M, Holberton J, Hunt RW, Jacobs SE, Kornberg AJ, Leventer RJ, Mandelstam S, McMahon JM, Mefford HC, Panetta J, Riseley J, Rodriguez-Casero V, Ryan MM, Schneider AL, Smith LJ, Stark Z, Wong F, Yiu EM, Scheffer IE, and Harvey AS
- Subjects
- Anticonvulsants therapeutic use, Child, Preschool, Cohort Studies, Developmental Disabilities etiology, Developmental Disabilities physiopathology, Disease Progression, Electroencephalography, Epilepsies, Myoclonic drug therapy, Epilepsies, Myoclonic etiology, Epilepsies, Myoclonic physiopathology, Epileptic Syndromes drug therapy, Epileptic Syndromes epidemiology, Epileptic Syndromes etiology, Epileptic Syndromes physiopathology, Female, Humans, Incidence, Infant, Infant, Newborn, Lennox Gastaut Syndrome drug therapy, Lennox Gastaut Syndrome epidemiology, Lennox Gastaut Syndrome etiology, Lennox Gastaut Syndrome physiopathology, Male, Malformations of Cortical Development complications, Malformations of Cortical Development epidemiology, Malformations of Cortical Development surgery, Mortality, Severity of Illness Index, Spasms, Infantile drug therapy, Spasms, Infantile etiology, Spasms, Infantile physiopathology, Victoria epidemiology, Developmental Disabilities epidemiology, Epilepsies, Myoclonic epidemiology, Spasms, Infantile epidemiology
- Abstract
Objective: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes., Methods: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined., Results: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased., Significance: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication., (© 2021 International League Against Epilepsy.)
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- 2021
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19. Neuronal ceroid lipofuscinosis type 2: an Australian case series.
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Johnson AM, Mandelstam S, Andrews I, Boysen K, Yaplito-Lee J, Fietz M, Nagarajan L, Rodriguez-Casero V, Ryan MM, Smith N, Scheffer IE, and Ellaway C
- Subjects
- Australia, Brain diagnostic imaging, Child, Child, Preschool, Electroencephalography, Humans, Retrospective Studies, Tripeptidyl-Peptidase 1, Neuronal Ceroid-Lipofuscinoses diagnostic imaging
- Abstract
Aim: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative disorder presenting in children aged 2-4 years with seizures and loss of motor and language skills, followed by blindness and death in late childhood. Initial presenting features are similar to a range of common epilepsies. We aim to highlight typical clinical and radiological features that may prompt diagnosis of CLN2 disease in early disease stages., Methods: We present a series of 13 Australian patients with CLN2 disease, describing clinical features, disease evolution, neuroimaging, electroencephalogram, biochemical and genetic results. Expert neuroradiological magnetic resonance imaging (MRI) analysis was retrospectively performed on 10 cases., Results: Twelve patients presented with seizures, with initial seizures being focal (n = 4), generalised tonic-clonic (n = 3), absence (n = 3) and febrile (n = 2). Eleven patients (85%) had a language delay before the onset of seizures. Cerebellar or cerebral atrophy was noted in all patients on centralised MRI review, with abnormalities of the brain-stem, ventricles, corpus callosum and hippocampi., Conclusions: Early language delay with the onset of seizures at 2-4 years of age is the hallmark of CLN2 disease. MRI findings of early subtle atrophy in the cerebellum or posterior cortical regions should hasten testing for CLN2 disease to enable early initiation of enzyme replacement therapy., (© 2020 The Authors Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)
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- 2020
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20. Cerebral hypomyelination associated with biallelic variants of FIG4.
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Lenk GM, Berry IR, Stutterd CA, Blyth M, Green L, Vadlamani G, Warren D, Craven I, Fanjul-Fernandez M, Rodriguez-Casero V, Lockhart PJ, Vanderver A, Simons C, Gibb S, Sadedin S, White SM, Christodoulou J, Skibina O, Ruddle J, Tan TY, Leventer RJ, Livingston JH, and Meisler MH
- Subjects
- Child, Child, Preschool, DNA Mutational Analysis, Demyelinating Diseases metabolism, Fibroblasts metabolism, Genotype, Humans, Inheritance Patterns, Magnetic Resonance Imaging, Male, Neuroimaging, Pedigree, Phenotype, Alleles, Demyelinating Diseases diagnosis, Demyelinating Diseases genetics, Flavoproteins genetics, Genetic Association Studies, Genetic Predisposition to Disease, Mutation, Phosphoric Monoester Hydrolases genetics
- Abstract
The lipid phosphatase gene FIG4 is responsible for Yunis-Varón syndrome and Charcot-Marie-Tooth disease Type 4J, a peripheral neuropathy. We now describe four families with FIG4 variants and prominent abnormalities of central nervous system (CNS) white matter (leukoencephalopathy), with onset in early childhood, ranging from severe hypomyelination to mild undermyelination, in addition to peripheral neuropathy. Affected individuals inherited biallelic FIG4 variants from heterozygous parents. Cultured fibroblasts exhibit enlarged vacuoles characteristic of FIG4 dysfunction. Two unrelated families segregate the same G > A variant in the +1 position of intron 21 in the homozygous state in one family and compound heterozygous in the other. This mutation in the splice donor site of exon 21 results in read-through from exon 20 into intron 20 and truncation of the final 115 C-terminal amino acids of FIG4, with retention of partial function. The observed CNS white matter disorder in these families is consistent with the myelination defects in the FIG4 null mouse and the known role of FIG4 in oligodendrocyte maturation. The families described here the expanded clinical spectrum of FIG4 deficiency to include leukoencephalopathy., (© 2019 Wiley Periodicals, Inc.)
- Published
- 2019
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21. Acute spinal cord syndrome secondary to venous congestion.
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Woodcock IR, Coscini N, Mandelstam S, Rodriguez-Casero V, and Dabscheck G
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- Acute Disease, Adolescent, Humans, Hyperemia diagnostic imaging, Hyperemia drug therapy, Male, Spinal Cord Diseases diagnostic imaging, Spinal Cord Diseases drug therapy, Syndrome, Hydroxides poisoning, Hyperemia complications, Potassium Compounds poisoning, Spinal Cord Diseases etiology
- Published
- 2016
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22. SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.
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Howell KB, McMahon JM, Carvill GL, Tambunan D, Mackay MT, Rodriguez-Casero V, Webster R, Clark D, Freeman JL, Calvert S, Olson HE, Mandelstam S, Poduri A, Mefford HC, Harvey AS, and Scheffer IE
- Subjects
- Adolescent, Brain Diseases complications, Child, Child, Preschool, Electroencephalography methods, Epilepsies, Partial complications, Female, Humans, Infant, Male, Phenotype, Seizures complications, Spasms, Infantile genetics, Young Adult, Brain Diseases genetics, Epilepsies, Partial genetics, Genetic Predisposition to Disease, Mutation genetics, NAV1.2 Voltage-Gated Sodium Channel genetics, Seizures genetics
- Abstract
Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy., Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping., Results: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one., Conclusions: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control., (© 2015 American Academy of Neurology.)
- Published
- 2015
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23. Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.
- Author
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Carvill GL, Heavin SB, Yendle SC, McMahon JM, O'Roak BJ, Cook J, Khan A, Dorschner MO, Weaver M, Calvert S, Malone S, Wallace G, Stanley T, Bye AM, Bleasel A, Howell KB, Kivity S, Mackay MT, Rodriguez-Casero V, Webster R, Korczyn A, Afawi Z, Zelnick N, Lerman-Sagie T, Lev D, Møller RS, Gill D, Andrade DM, Freeman JL, Sadleir LG, Shendure J, Berkovic SF, Scheffer IE, and Mefford HC
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Epilepsy diagnosis, Epilepsy epidemiology, Female, Genetic Predisposition to Disease genetics, Humans, Male, Young Adult, DNA Mutational Analysis methods, DNA-Binding Proteins genetics, Epilepsy genetics, Mutation physiology, ras GTPase-Activating Proteins genetics
- Abstract
Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort. Six of the 46 candidate genes had 1 or more pathogenic variants, collectively accounting for 3% of our cohort. We show that de novo CHD2 and SYNGAP1 mutations are new causes of epileptic encephalopathies, accounting for 1.2% and 1% of cases, respectively. We also expand the phenotypic spectra explained by SCN1A, SCN2A and SCN8A mutations. To our knowledge, this is the largest cohort of cases with epileptic encephalopathies to undergo targeted resequencing. Implementation of this rapid and efficient method will change diagnosis and understanding of the molecular etiologies of these disorders.
- Published
- 2013
- Full Text
- View/download PDF
24. Guillain-Barré syndrome following pandemic (H1N1) 2009 influenza A immunisation in Victoria: a self-controlled case series.
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Crawford NW, Cheng A, Andrews N, Charles PG, Clothier HJ, Day B, Day T, Gates P, Macdonell R, Roberts L, Rodriguez-Casero V, Wijeratne T, and Kiers L
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Guillain-Barre Syndrome etiology, Humans, Incidence, Male, Middle Aged, Pandemics, Population Surveillance, Research Design, Risk, Victoria epidemiology, Young Adult, Guillain-Barre Syndrome epidemiology, Influenza A Virus, H1N1 Subtype, Influenza Vaccines adverse effects, Influenza, Human prevention & control
- Abstract
Objectives: To determine the relative incidence (RI) of Guillain-Barré syndrome (GBS) in a single Australian state following pandemic (H1N1) 2009 influenza A immunisation (monovalent vaccine or seasonal trivalent influenza vaccine [TIV]) in 2009-2010., Design, Setting and Participants: Active GBS surveillance (cases assessed by two neurologists according to the Brighton criteria) from 30 September 2009 to 30 September 2010, conducted at 10 hospitals in Victoria, Australia., Main Outcome Measures: The RI of GBS in the risk window of 0-42 days after vaccination., Results: Sixty-six potential GBS cases were identified, with complete data on 50 confirmed cases. The Victorian annual incidence of GBS was 1.7 per 100 000 population. Three cases had received monovalent vaccine and one case had received seasonal TIV within 42 days of symptom onset. The RI of GBS following monovalent vaccination was 3.4 (95% CI, 0.8-15.0). For TIV, there was one case in the risk period (RI, 0.69; 95% CI, 0.08-5.64)., Conclusions: This is the first published study reviewing GBS after a trivalent and/or monovalent influenza vaccine containing the pandemic (H1N1) 2009 strain, with only a small proportion of GBS cases occurring after influenza immunisation. H1N1-containing vaccines were not statistically associated with GBS, but this study could not exclude smaller increases in the RI. Active surveillance of adverse events following immunisation is required to maintain public and health care professional confidence in mass vaccine implementation programs.
- Published
- 2012
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