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51. Prevalence and management of gastrointestinal manifestations in Silver–Russell syndrome

Author

Marsaud, Céline, Rossignol, Sylvie, Tounian, Patrick, Netchine, Irène, Dubern, Béatrice, Abadie, V, Alcayde, S, Alembik, Y, Amiel, J, Baujat, G, Baumann-Morel, C, Bieth, E, Bertrand, AM, Bonneau, D, Bouhours Nouet, N, Brachet, C, Brioude, F, Brossier, JP, Boute, O, Cabrol, S, Carel, JC, Chabrol, B, Chivu, O, Christin, P, Collignon, P, Cordier, MP, Cormier Daire, V, Coubes, C, Coupe, B, Coutant, R, Craen, M, Crosnier, H, De Baufort, C, David, A, Delahaye, A, Delobel, B, Delrue, MA, Dieux Coeslier, A, Dommergues, MA, Doray, B, Duban-Bedu, B, Dufresne, S, Edery, P, Esteva, B, Farges, C, Fechtner, I, Francannet, C, Gilbert Dussardier, B, Gilbert, B, Ginglinger, E, Giullano, F, Goldenberg, A, Hamiel, O, Harbison, MD, Heinrichs, C, Heron, D, Holder, M, Houang, M, Genevieve, D, Gerard, M, Gonzales, M, Jantchou, P, Jonveaux, P, Jouk, PS, Kurtz, F, Le Bouc, Y, Le Merrer, M, Linglart, A, Leheup, B, Lebrun, M, Leger, J, Leinhart, A, Loeuille, GA, Manouvrier, S, Martin-Coignard, D, Mas, JC, Mathieu, M, Mercier, S, Mignot, B, Morice-Picard, F, Morin, G, Newfield, R, Odent, S, Oliver-Petit, I, Olivier-Faivre, L, Petriczko, E, Philip, N, Pienkowski, C, Pinson, L, Pinto, G, Polak, M, Quelin, C, Port-lis, M, Reiter, JC, Rio, M, Riviere, MF, Roquelaure, B, Salem, J, Simon, D, Soskin, S, Sznajer, Y, Tauber, M, Thauvin, C, Touraine, R, Teinturier, C, Toutain, A, Van Maldergem, L, Verloes, A, Vincent Delorme, C, Vu-Hong, T-A, and Weill, J

Published
2015
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54. Systematic molecular and cytogenetic screening of 100 patients with marfanoid syndromes and intellectual disability

Author

Callier, P, Aral, B, Hanna, N, Lambert, S, Dindy, H, Ragon, C, Payet, M, Collod-Beroud, G, Carmignac, V, Delrue, M A, Goizet, C, Philip, N, Busa, T, Dulac, Y, Missotte, I, Sznajer, Y, Toutain, A, Francannet, C, Megarbane, A, Julia, S, Edouard, T, Sarda, P, Amiel, J, Lyonnet, S, Cormier-Daire, V, Gilbert, B, Jacquette, A, Heron, D, Collignon, P, Lacombe, D, Morice-Picard, F, Jouk, P S, Cusin, V, Willems, M, Sarrazin, E, Amarof, K, Coubes, C, Addor, M C, Journel, H, Colin, E, Van Kien, Khau P, Baumann, C, Leheup, B, Coignard, Martin- D, Doco-Fenzy, M, Goldenberg, A, Plessis, G, Thevenon, J, Pasquier, L, Odent, S, Vabres, P, Huet, F, Marle, N, Boidron, Mosca- AL, Mugneret, F, Gauthier, S, Binquet, C, Thauvin-Robinet, C, Jondeau, G, Boileau, C, and Faivre, L

Published
2013
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55. Fetoscopic insufflation modeled in the extrauterine environment for neonatal development (EXTEND): Fetoscopic insufflation is safe for the fetus

Author

Marcus G. Davey, Ali Y. Mejaddam, Heron D. Baumgarten, James Moon, Kendall M. Lawrence, Katsusuke Ozawa, Aimee G Kim, Barbara E. Coons, Avery C. Rossidis, Ryne A. Didier, Anush Sridharan, Felix De Bie, and Alan W. Flake

Subjects
Insufflation, Amniotic fluid, Meningomyelocele, medicine.medical_treatment, Umbilical cord, Fetoscopy, 03 medical and health sciences, 0302 clinical medicine, Fetus, Pregnancy, 030225 pediatrics, medicine, Animals, Sheep, medicine.diagnostic_test, business.industry, Fetal surgery, Gestational age, General Medicine, Carbon Dioxide, Fetal Diseases, medicine.anatomical_structure, In utero, 030220 oncology & carcinogenesis, Anesthesia, Pediatrics, Perinatology and Child Health, Surgery, Female, business
Abstract

Background Minimally invasive fetal surgery, or fetoscopy, is an alternative to open fetal surgery to repair common birth defects like myelomeningocele. Although this hysterotomy-sparing approach reduces maternal morbidity, the effects of in utero insufflation on the fetus are poorly understood. Our purpose was to determine the optimal fetal insufflation conditions. Methods Fetal sheep at gestational age 104 to 107 days were studied under insufflation conditions in utero and ex utero. The ex utero fetuses were cannulated via their umbilical vessels into a support device, the EXTra-uterine Environment for Neonatal Development (EXTEND). EXTEND fetuses were exposed to four different insufflation conditions for four hours: untreated carbon dioxide (CO2) (n = 5), warm humidified (whCO2) (n = 4), whCO2 with the umbilical cord exposed (n = 3), and whCO2 without amniotic fluid (skin and cord exposed) (n = 3). Results In utero insufflation led to significant increases in fetal CO2 and reductions in fetal pH. Ex utero insufflation with whCO2 did not lead to changes in fetal blood gas measurements or cerebral perfusion parameters. Insufflation with whCO2 with an exposed umbilical cord led to reduced umbilical blood flow. Conclusions Insufflation with warm humidified CO2 with an amniotic fluid covered umbilical cord is well tolerated by the fetus without significant changes in hemodynamics or cerebral perfusion parameters. Type of study Basic science Level of evidence N/A

Published
2020

56. Bilateral papillary thyroid cancer in children: Risk factors and frequency of postoperative diagnosis

Author

Tricia R. Bhatti, Andrew J. Bauer, Ken Kazahaya, Sogol Mostoufi-Moab, N. Scott Adzick, Carolyn M. Jenks, Amber Isaza, and Heron D. Baumgarten

Subjects
Male, medicine.medical_specialty, endocrine system diseases, Adolescent, Lymphovascular invasion, Papillary thyroid cancer, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, 030225 pediatrics, medicine, Humans, Postoperative Period, Thyroid Neoplasms, Child, Retrospective Studies, Ultrasonography, Total thyroidectomy, business.industry, Incidence (epidemiology), Ultrasound, Nodule (medicine), General Medicine, medicine.disease, Occult, Clinical research, Treatment Outcome, Thyroid Cancer, Papillary, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Pediatrics, Perinatology and Child Health, Thyroidectomy, Surgery, Female, Radiology, medicine.symptom, business
Abstract

Background The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Evaluating this assumption, we reviewed the characteristics of bilateral PTC in a large cohort of children. Methods A retrospective chart review for patients surgically treated for PTC from 2009 to 2018 analyzing preoperative risk factors, ultrasound findings, and pathology results was performed. Bilateral disease was defined as pathologic PTC in the contralateral lobe, including microscopic disease. Results Of the 172 patients included, 38.4% had bilateral disease with 23% diagnosed postoperatively. Multifocal disease on ultrasound was associated with bilateral disease (OR 2.9, 95% CI 1.5–5.9, p = 0.002). Nodule dimension > 2 cm was associated with increased risk for postoperative bilateral disease (OR 3.5, 95% CI 1.6–7.4, p = 0.001). Patients with bilateral disease were more likely to have extrathyroidal extension, lymphovascular invasion, positive central lymph nodes, and extranodal extension (p Conclusion Thirty-eight percent of children were diagnosed with PTC demonstrate bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. Thus, TT is the appropriate surgical approach for pediatric patients with PTC. Type of Study Clinical Research, Retrospective Review. Level of Evidence Level IV.

Published
2020

57. A Rabbit Model for Optimization of Amniotic Fluid Components in the EXTrauterine Environment for Newborn Development (EXTEND) System

Author

Heron D. Baumgarten, Zoya Butt, Heather A. Hartman, Marcus G. Davey, Kendall M. Lawrence, Aimee G. Kim, Katsusuke Ozawa, Alan W. Flake, and Avery C. Rossidis

Subjects
Embryology, Amniotic fluid, Andrology, Fetal Development, Animal model, Bacterial colonization, Pregnancy, Medicine, Animals, Radiology, Nuclear Medicine and imaging, Fetus, business.industry, Ultrasound, Obstetrics and Gynecology, Uterine horns, General Medicine, Amniotic Fluid, Intestines, Disease Models, Animal, Fetal Weight, Pediatrics, Perinatology and Child Health, Rabbit model, Gestation, Female, Rabbits, business
Abstract

In this model article, we present a protocol for continuous amniotic fluid exchange in rabbits using a novel system to test the effects of growth factor-deficient, artificial amniotic fluid on bowel development. Background: Ideally, the EXTrauterine Environment for Neonatal Development (EXTEND) will provide physiologic support to the extreme premature infant. An important component of that environment is the amniotic fluid. Thus, we developed an animal model to study the growth factors found within amniotic fluid and inform design of a synthetic fluid to optimize fetal development. Methods: We designed a model of amniotic fluid exchange within the pregnant rabbit, continuously removing the natural fluid from around 2 fetuses per doe and replacing it with a physiologic electrolyte solution during the final 100 h of gestation. Two fetuses from the contralateral uterine horn were used as sham-operated controls. Thirty-eight fetuses were analyzed, 19 in each group. We analyzed the fetal growth and bowel development. Results: Ultrasound after 100 h of exchange showed equivalent fluid volumes, p = 0.63. Cultures were negative for bacterial colonization. Final fluid protein concentrations were 11.6% that of control fluid (mean 1,451 ± 224.2 vs. 12,491 ± 849.2 μg/mL). There was no significant difference in fetal growth, with experimental weights 91.4% of control weights, p = 0.07. Fetal bowel weights (90.1%, p = 0.16) and lengths (94.2%, p = 0.49) were also not significantly less compared to controls. There was no significant difference in villous height or crypt depth measurements between the groups, and absorptive capacity of the bowel was not different between groups, p = 0.44. Conclusion: This animal model allows for manipulation of the components of amniotic fluid. Marked reduction of natural amniotic fluid proteins during gestation does not appear to significantly impair fetal growth or bowel development. Further work with this model will assess the importance of amniotic fluid components for normal development to inform design of a synthetic fluid for use during EXTEND.

Published
2020

58. Integrated genome and transcriptome analyses solves about one third of the patients with rare developmental disorders and negative first-line molecular investigations

Author

Vitobello, A., Mau-Them, F. Tran, Bruel, A. L., Duffourd, Y., Tisserant, E., Callier, P., Moutton, S., Nambot, S., Lehalle, D., Jean-Marcais, N., Delanne, J., Racine, C., Thevenon, J., Poe, C., Jouan, T., Chevarin, M., Willems, M., Coubes, C., Genevieve, D., Houcinat, N., Masurel-Paulet, Alice, Mosca-Boidron, A.-L., Sorlin, A., Isidor, B., Heide, S., Afenjar, A., Rodriguez, D., Mignot, C., Heron, D., Vincent, M., Charles, P., Odent, S., Dubourg, C., Faudet, A., Keren, B., Cogne, B., Boland, A., Olaso, R., Philippe, C., Deleuze, J. F., Faivre, L., Thauvin-Robinet, C., Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lapeyronie [Montpellier] (CHU), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Université Paris 1 Panthéon-Sorbonne (UP1), CHU Pontchaillou [Rennes], 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), Université Paris-Saclay, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and 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 )

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2020
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59. Evaluation of DNA Methylation Episignatures for Diagnosis and Phenotype Correlations in 42 Mendelian Neurodevelopmental Disorders

Author

Aref-Eshghi, E., Kerkhof, J., Pedro, V.P., Barat-Houari, M., Ruiz-Pallares, N., Andrau, J.C., Lacombe, D., Van-Gils, J., Fergelot, P., Dubourg, C., Cormier-Daire, V., Rondeau, S., Lecoquierre, F., Saugier-Veber, P., Nicolas, G., Lesca, G., Chatron, N., Sanlaville, D., Vitobello, A., Faivre, L., Thauvin-Robinet, C., Laumonnier, F., Raynaud, M., Alders, M., Mannens, M., Henneman, P., Hennekam, R.C., Velasco, G., Francastel, C., Ulveling, D., Ciolfi, A., Pizzi, S., Tartaglia, M., Heide, S. van der, Heron, D., Mignot, C., Keren, B., Whalen, S., Afenjar, A., Bienvenu, T., Campeau, P.M., Rousseau, J., Levy, M.A., Brick, L., Kozenko, M., Balci, T.B., Siu, V.M., Stuart, A., Kadour, M., Masters, J., Takano, K., Kleefstra, T., Leeuw, N. de, Field, M., Shaw, M., Gecz, J., Ainsworth, P.J., Lin, H., Rodenhiser, D.I., Friez, M.J., Tedder, M., Lee, Jae Lyun, DuPont, B.R., Stevenson, R.E., Skinner, S.A., Schwartz, C.E., Genevieve, D., Sadikovic, B., Aref-Eshghi, E., Kerkhof, J., Pedro, V.P., Barat-Houari, M., Ruiz-Pallares, N., Andrau, J.C., Lacombe, D., Van-Gils, J., Fergelot, P., Dubourg, C., Cormier-Daire, V., Rondeau, S., Lecoquierre, F., Saugier-Veber, P., Nicolas, G., Lesca, G., Chatron, N., Sanlaville, D., Vitobello, A., Faivre, L., Thauvin-Robinet, C., Laumonnier, F., Raynaud, M., Alders, M., Mannens, M., Henneman, P., Hennekam, R.C., Velasco, G., Francastel, C., Ulveling, D., Ciolfi, A., Pizzi, S., Tartaglia, M., Heide, S. van der, Heron, D., Mignot, C., Keren, B., Whalen, S., Afenjar, A., Bienvenu, T., Campeau, P.M., Rousseau, J., Levy, M.A., Brick, L., Kozenko, M., Balci, T.B., Siu, V.M., Stuart, A., Kadour, M., Masters, J., Takano, K., Kleefstra, T., Leeuw, N. de, Field, M., Shaw, M., Gecz, J., Ainsworth, P.J., Lin, H., Rodenhiser, D.I., Friez, M.J., Tedder, M., Lee, Jae Lyun, DuPont, B.R., Stevenson, R.E., Skinner, S.A., Schwartz, C.E., Genevieve, D., and Sadikovic, B.

Abstract

Contains fulltext : 218274.pdf (Publisher’s version ) (Closed access), Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called "episignatures"). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight their key features as they are related to genetic heterogeneity, dosage effect, unaffected carrier status, and incomplete penetrance. We demonstrate the necessity of multiclass modeling for accurate genetic variant classification and show how disease classification using a single episignature at a time can sometimes lead to classification errors in closely related episignatures. We demonstrate the utility of this tool in resolving ambiguous clinical cases and identification of previously undiagnosed cases through mass screening of a large cohort of subjects with developmental delays and congenital anomalies. This study more than doubles the number of published syndromes with DNA methylation episignatures and, most significantly, opens new avenues for accurate diagnosis and clinical assessment in individuals affected by these disorders.

Published
2020

60. Callosal agenesis and congenital mirror movements: outcomes associated with DCC mutations

Author

Spencer-Smith, M, Knight, JL, Lacaze, E, Depienne, C, Lockhart, PJ, Richards, LJ, Heron, D, Leventer, RJ, Robinson, GA, Ceslis, A, Gibson, E, Giraudat, K, McIlroy, A, Paul, LK, Siffredi, V, Bahlo, M, Barker, M, Blondiaux, E, Edwards, TJ, Garel, C, Heide, S, Keren, B, Mandelstam, SA, Marsh, APL, McGillivray, G, Mignot, C, Moutard, M-L, Nava, C, Pope, K, Rastetter, A, Stephenson, SEM, Valence, S, de Villemeur, TB, Wood, A, Anderson, V, Sherr, EH, Spencer-Smith, M, Knight, JL, Lacaze, E, Depienne, C, Lockhart, PJ, Richards, LJ, Heron, D, Leventer, RJ, Robinson, GA, Ceslis, A, Gibson, E, Giraudat, K, McIlroy, A, Paul, LK, Siffredi, V, Bahlo, M, Barker, M, Blondiaux, E, Edwards, TJ, Garel, C, Heide, S, Keren, B, Mandelstam, SA, Marsh, APL, McGillivray, G, Mignot, C, Moutard, M-L, Nava, C, Pope, K, Rastetter, A, Stephenson, SEM, Valence, S, de Villemeur, TB, Wood, A, Anderson, V, and Sherr, EH

Abstract

Pathogenic variants in the gene encoding deleted in colorectal cancer (DCC) are the first genetic cause of isolated agenesis of the corpus callosum (ACC). Here we present the detailed neurological, brain magnetic resonance imaging (MRI), and neuropsychological characteristics of 12 individuals from three families with pathogenic variants in DCC (aged 8-50y), who showed ACC and mirror movements (n=5), mirror movements only (n=2), ACC only (n=3), or neither ACC nor mirror movements (n=2). There was heterogeneity in the neurological and neuroimaging features on brain MRI, and performance across neuropsychological domains ranged from extremely low (impaired) to within normal limits (average). Our findings show that ACC and/or mirror movements are associated with low functioning in select neuropsychological domains and a DCC pathogenic variant alone is not sufficient to explain the disability. WHAT THIS PAPER ADDS: Neuropsychological impairment severity is related to presence of mirror movements and/or agenesis of the corpus callosum. A DCC pathogenic variant in isolation is associated with the best prognosis.

Published
2020

61. CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects

Author

Nasser, H., Vera, L., Elmaleh-Berges, M., Steindl, K., Letard, P., Teissier, N., Ernault, A., Guimiot, F., Afenjar, A., Moutard, M. L., Heron, D., Alembik, Y., Momtchilova, M., Milani, P., Kubis, N., Pouvreau, N., Zollino, Marcella, Guilmin Crepon, S., Kaguelidou, F., Gressens, P., Verloes, A., Rauch, A., El Ghouzzi, V., Drunat, S., Passemard, S., Zollino M. (ORCID:0000-0003-4871-9519), Nasser, H., Vera, L., Elmaleh-Berges, M., Steindl, K., Letard, P., Teissier, N., Ernault, A., Guimiot, F., Afenjar, A., Moutard, M. L., Heron, D., Alembik, Y., Momtchilova, M., Milani, P., Kubis, N., Pouvreau, N., Zollino, Marcella, Guilmin Crepon, S., Kaguelidou, F., Gressens, P., Verloes, A., Rauch, A., El Ghouzzi, V., Drunat, S., Passemard, S., and Zollino M. (ORCID:0000-0003-4871-9519)

Abstract

Background: Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH forms at the clinical level. Methods: 7 patients with newly identified mutations in CDK5RAP2 (MCPH3) were investigated by performing prospective, extensive and systematic clinical, MRI, psychomotor, neurosensory and cognitive examinations under similar conditions. Results: All patients displayed neurosensory defects in addition to microcephaly. Small cochlea with incomplete partition type II was found in all cases and was associated with progressive deafness in 4 of them. Furthermore, the CDK5RAP2 protein was specifically identified in the developing cochlea from human fetal tissues. Microphthalmia was also present in all patients along with retinal pigmentation changes and lipofuscin deposits. Finally, hypothalamic anomalies consisting of interhypothalamic adhesions, a congenital midline defect usually associated with holoprosencephaly, was detected in 5 cases. Conclusion: This is the first report indicating that CDK5RAP2 not only governs brain size but also plays a role in ocular and cochlear development and is necessary for hypothalamic nuclear separation at the midline. Our data indicate that CDK5RAP2 should be considered as a potential gene associated with deafness and forme fruste of holoprosencephaly. These children should be given neurosensory follow-up to prevent additional comorbidities and allow them reaching their full educational potential. Trial registration number: NCT01565005.

Published
2020

62. Developmental and symptom profiles in early-onset psychosis

Author

Ferrafiat, Vladimir, Raffin, Marie, Freri, Elena, Granata, Tiziana, Nardocci, Nardo, Zibordi, Federica, Bodeau, Nicolas, Benarous, Xavier, Olliac, Bertrand, Riquin, Elise, Viaux, Sylvie, Haroche, Julien, Amoura, Zahir, Gérardin, Priscille, Consoli, Angèle, Zahoui, Mohamed, Zhou, Bo, Bilan, Frederic, Zhang, Xianglong, Gilbert-Dussardier, Brigitte, Viaux-Savelon, Sylvie, Pattni, Reenal, Ho, Steve, Urban, Alexander, Delion, Pierre, Labreuche, Julien, Deplanque, Dominique, Duhamel, Alain, Lallié, Céline, Ravary, Maud, Goëb, Jean-Louis, Medjkane, François, Gauthier, Soizic, Anzalone, Salvatore, Zaoui, Mohamed, Chetouani, Mohamed, Villa, François, Berthoz, Alain, Angeard, N., Huerta, E., Gargiulo, M., Servais, L., Eymard, B., Chérot, E., Keren, B., Dubourg, C., Carré, W., Fradin, M., Lavillaureix, A., Afenjar, A., Burglen, L., Whalen, S., Charles, P., Marey, I., Heide, S., Jacquette, A., Heron, D., Doummar, D., Rodriguez, D., Billette de Villemeur, T., Moutard, M.-L., Guët, A., Périsse, D., Demurger, F., Quelin, C., Depienne, C., Odent, S., Nava, C., David, V., Pasquier, L., Mignot, C., Giannitelli, Marianna, Levinson, Douglas, Cohen, David, Xavier, Jean, Laurent-Levinson, Claudine, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut des Systèmes Intelligents et de Robotique (ISIR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroépidémiologie Tropicale (NET), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Fédération hospitalo-universitaire de psychiatrie de l'enfant et de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Stanford University, Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire de Neurosciences Fonctionnelles et Pathologies (LNFP), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Perception, Interaction, Robotique sociales (PIROS), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Physiologie de la Perception et de l'Action (LPPA), Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD [France-Ouest]), Service: neuropédiatrie pathologie du développement, Université Pierre et Marie Curie - Paris 6 (UPMC), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, National Alliance for Research on Schizophrenia and Depression, Centre de Référence des Maladies Rares à Expression Psychiatrique, Department of Child and Adolescent Psychiatry, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Stanford Schizophrenia Genetics Research Fund, Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), 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 Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Service de génétique clinique, and hôpital Sud

Subjects
Adult, Psychosis, Adolescent, Early onset psychosis, 03 medical and health sciences, [SCCO]Cognitive science, 0302 clinical medicine, Cluster analysis, Humans, Medicine, Medical diagnosis, Child, Children, Biological Psychiatry, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Psychopathology, business.industry, Neuropsychology, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Symptom profiles, Psychotic Disorders, Schizophrenia, Cohort, Factor analysis, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

Psychotic disorders in children are more heterogeneous than is captured by categorical diagnoses. In a new cohort of children and adolescents, we evaluated the relationships among age at onset (AAO), clinical symptoms and developmental impairments. Patients with schizophrenia and other "spectrum" psychotic diagnoses (N = 88; AAO 6-17, mean 12.6) were evaluated with diagnostic interviews, a new clinical scale (Lifetime Dimensions of Psychosis Scale-Child and Adolescent), and neuropsychological and medical evaluations. Key findings were replicated in an adult cohort of 2420 cases, including 127 with retrospective AAO13. Factor and cluster analyses were carried out to identify clinical profiles. Five clinical factors were identified in each cohort: Positive, Bizarre Positive, Negative/Formal Thought Disorder, Depression and Mania. Earlier AAO predicted severity of bizarre positive symptoms in children and of bizarre and other symptoms in adults. Four clinical clusters in the child cohort were characterized by: more severe bizarre positive symptoms (N = 31); negative symptoms (N = 15); premorbid autism spectrum features and developmental delay (N = 12); and depressive symptoms with heterogeneous diagnoses and mild positive/negative symptoms (N = 25). Previous factor-analytic studies of childhood psychosis did not specifically consider bizarre positive symptoms. Here, bizarre positive symptoms emerged as clinical markers of severe, childhood-onset psychosis similar to adult schizophrenia. The four clusters are clinically meaningful and useful for treatment planning and potentially for biological research. Childhood-onset cases are rare and thus difficult to study, but additional, larger cohorts may be useful in dissecting the biological and developmental heterogeneity of psychotic disorders.

Published
2019
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63. Preemptive Delivery and Immediate Resection for Fetuses with High-Risk Sacrococcygeal Teratomas

Author

Heron D. Baumgarten, N. Scott Adzick, Julie S. Moldenhauer, Juliana Gebb, Holly L. Hedrick, Mark P. Johnson, William H. Peranteau, Alan W. Flake, and Nahla Khalek

Subjects
Embryology, Fetus, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, Fetal surgery, business.industry, medicine.medical_treatment, Obstetrics and Gynecology, General Medicine, medicine.disease, Mirror syndrome, Surgery, 03 medical and health sciences, Pulmonary hypoplasia, 0302 clinical medicine, In utero, embryonic structures, Pediatrics, Perinatology and Child Health, medicine, Gestation, Radiology, Nuclear Medicine and imaging, Decompensation, 030212 general & internal medicine, Sacrococcygeal teratoma, business
Abstract

Introduction: Fetuses with “high-risk” sacrococcygeal teratoma (SCT) have a mortality rate of 40–50%. While fetal surgery may benefit select fetuses prior to 27 weeks’ gestation, many fetuses die due to consequences of rapid tumor growth after 27 weeks. Here we report our experience applying “preemptive” delivery to fetuses who manifest signs of decompensation between 27 and 32 weeks. Methods: A retrospective review of SCT fetuses delivered between 2010 and 2016 at ≤32 weeks’ gestation was performed. Patients who decompensated prior to 27 weeks and were treated with fetal surgery or neonatal palliation were excluded. Results: Forty-two SCT fetuses were evaluated, and 11 were preemptively delivered in response to impending fetal or maternal decompensation. Nine (81.8%) survived. One death was due to pulmonary hypoplasia in a neonate with significant intra-abdominal tumor burden, and the other was due to in utero tumor rupture. There were no deaths related to prematurity in this cohort. Conclusions: Many fetuses with SCT manifest signs of decompensation between 27 and 32 weeks. In the absence of fetal hydrops prior to 27 weeks or tumor rupture in utero, early delivery is associated with favorable outcomes. Our single-center experience supports a management algorithm change to incorporate “preemptive” delivery for selected cases.

Published
2018
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67. Evidence of infection of cassava plants with the begomovirus passionfruit severe leaf distortion virus in Brazil

Author

Camila Geovana Ferro, Gabriel Madoglio Favara, Heron Delgado Kraide, Naasoon Luiz Santos Mesquita, Quelmo Silva de Novaes, and Jorge Alberto Marques Rezende

Subjects
PSLDV, first report, complete genome, root crop, natural infection, Agriculture (General), S1-972
Abstract

ABSTRACT Symptoms of severe vein clearing, leaf rolling, and blistering were observed in cassava plants in southwestern Bahia State, Brazil. The plants were collected, vegetatively propagated, and kept in a greenhouse. Leaf samples tested positive for begomovirus infection by Polymerase chain reaction (PCR). Complete nucleotide sequences of DNA-A and DNA-B of isolate PSLDV-Man04 revealed 99.89 % and 96.2 % identity, respectively, with the bipartite begomovirus passionfruit severe leaf distortion virus (PSLDV) genome. This PSLDV isolate was experimentally transmitted to two and four of the five cassava plants and ten passion fruit plants, respectively, inoculated with Bemisia tabaci Middle East-Asia Minor 1 (MEAM1). This is the first report of the natural infection of cassava plants by the PSLDV begomovirus in Brazil.

Published
2024
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72. Mutation Update for the CSB/ERCC6 and CSA/ERCC8 Genes Involved in Cockayne Syndrome

Author

Laugel, V., Dalloz, C., Durand, M., Sauvanaud, F., Kristensen, U., Vincent, M. C., Pasquier, L., Odent, S., Cormier-Daire, V., Gener, B., Tobias, E. S., Tolmie, J. L., Martin-Coignard, D., Drouin-Garraud, V., Heron, D., Journel, H., Raffo, E., Vigneron, J., Lyonnet, S., Murday, V., Gubser-Mercati, D., Funalot, B., Brueton, L., del Pozo, Sanchez J., Muñoz, E., Gennery, A. R., Salih, M., Noruzinia, M., Prescott, K., Ramos, L., Stark, Z., Fieggen, K., Chabrol, B., Sarda, P., Edery, P., Bloch-Zupan, A., Fawcett, H., Pham, D., Egly, J. M., Lehmann, A. R., Sarasin, A., and Dollfus, H.

Published
2010
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74. Premature Lambs Exhibit Normal Mitochondrial Respiration after Long-Term Extrauterine Support.

Author

Rossidis, Avery C., Angelin, Alessia, Lawrence, Kendall M., Baumgarten, Heron D., Kim, Aimee G., Mejaddam, Ali Y., Coons, Barbara E., Hartman, Heather A., Hwang, Grace, Monos, Stylianos, Peranteau, William H., Davey, Marcus G., Murdock, Deborah, Wallace, Douglas C., Flake, Alan W., Rossidis, Avery C, Lawrence, Kendall M, Baumgarten, Heron D, Kim, Aimee G, and Mejaddam, Ali Y

Subjects
PREMATURE infants, MITOCHONDRIAL physiology, CELL respiration, ECTOPIC pregnancy, GESTATIONAL age
Abstract

Background: In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants.Objectives: We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level.Methods: Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105-107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3-4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128-134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured.Results: There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed.Conclusions: Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity. [ABSTRACT FROM AUTHOR]

Published
2019
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76. Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families

Author

Willems, M., Genevieve, D., Borck, G., Baumann, C., Baujat, G., Bieth, E., Edery, P., Farra, C., Gerard, M., Heron, D., Leheup, B., Le Merrer, M., Lyonnet, S., Martin-Coignard, D., Mathieu, M., Thauvin-Robinet, C., Verloes, A., Colleaux, L., Munnich, A., and Cormier-Daire, V.

Subjects
Seckel syndrome -- Genetic aspects, Seckel syndrome -- Research, Seckel syndrome -- Risk factors, Gene mutations -- Research, Health
Published
2010

78. Neurologic outcomes of the premature lamb in an extrauterine environment for neonatal development

Author

Marcus G. Davey, Aimee Kim, Grace Hwang, Kendall M. Lawrence, Kathleen Young, Arastoo Vossough, Emily A. Partridge, Patrick E. McGovern, Heron D. Baumgarten, Ali Y. Mejaddam, Avery C. Rossidis, Alan W. Flake, Alexander J. Schupper, Ryne A. Didier, Matthew A. Hornick, and William H. Peranteau

Subjects
Pediatrics, medicine.medical_specialty, Ischemia, Cerebral palsy, White matter, 03 medical and health sciences, Myelin, 0302 clinical medicine, Fetus, 030225 pediatrics, medicine, Animals, Myelin Sheath, Sheep, Domestic, Sheep, medicine.diagnostic_test, business.industry, Brain, Magnetic resonance imaging, General Medicine, medicine.disease, Magnetic Resonance Imaging, Neurologic injury, medicine.anatomical_structure, Animals, Newborn, 030220 oncology & carcinogenesis, Pediatrics, Perinatology and Child Health, Intensive Care, Neonatal, Gestation, Premature Birth, Surgery, business
Abstract

Background/Purpose Neurologic injury remains the most important morbidity of prematurity. Those born at the earliest gestational ages can face a lifetime of major disability. Perinatal insults result in developmental delay, cerebral palsy, and other profound permanent neurologic impairments. The EXTracorporeal Environment for Neonatal Development (EXTEND) aims to transition premature neonates through this sensitive period, but it's impact on neurologic development requires analysis. Methods Fetal sheep were maintained in a fluid-filled environment for up to 28 days. Physiologic parameters were measured continuously; tissues were subsequently fixed and preserved for myelin quantification, glial cell staining, and structural assessment via magnetic resonance. Surviving animals were functionally assessed. Results No evidence of fetal brain ischemia or white matter tract injury associated with the EXTEND system was detected, and the degree of myelination was regionally appropriate and consistent with age matched controls. No evidence of neurologic injury or immaturity was visible on magnetic resonance; animals that transitioned from the system had no persistent neurologic deficits. Conclusions No evidence of major neurologic morbidity was found in animals supported on the EXTEND system, though more work needs to be done in order to verify its safety during critical periods of neurologic development.

Published
2019

79. A recurrent de novo PACS2 heterozygous missense variant causes neonatal-onset developmental epileptic encephalopathy, facial dysmorphism and cerebellar dysgenesis

Author

Jean-Marcais, N., Olson, H. E., Yang, E., Heron, D., Tatton-Brown, K., van der Zwaag, P. A., Bijlsma, E. K., Krock, B. L., Backer, E., Kamsteeg, E., Sinnema, M., Reijnders, M. R. F., Bearden, D., Lunsing, R. J., Burglen, L., Lesca, G., Smith, L. A., Sheidley, B., Pearl, P. L., El Achkar, C. Moufawad, Poduri, A., Skraban, C. M., Nesbitt, A. I., van de Putte, D. E. Fransen, Ruivenkamp, C. A. L., Rump, P., Sabatier, I., Sweetser, D. A., Waxler, J. L., Tarpinian, J., Wierenga, K. J., Donadieu, J., Narayanan, V., Ramsey, K. M., Nava, C., Lelieveld, S. H., Schuurs-Hoeijmakers, J., Brunner, H. G., Keren, B., Mau-Them, F. Tran, Thevenon, J., Faivre, L., Thomas, G., and Thauvin-Robinet, C.

Published
2019

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

Author

Salpietro, V. Dixon, C.L. Guo, H. Bello, O.D. 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, G.B. Armstrong-Moron, J. Gueden, S. Bar-Yosef, O. Tzadok, M. Monaghan, K.G. Santiago-Sim, T. Person, R.E. Cho, M.T. Willaert, R. Yoo, Y. Chae, J.-H. Quan, Y. Wu, H. Wang, T. Bernier, R.A. Xia, K. Blesson, A. Jain, M. Motazacker, M.M. Jaeger, B. Schneider, A.L. Boysen, K. Muir, A.M. Myers, C.T. Gavrilova, R.H. Gunderson, L. Schultz-Rogers, L. Klee, E.W. 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. Hanna, M.G. Bugiardini, E. Hostettler, I. O’Callaghan, B. Khan, A. Cortese, A. O’Connor, E. Yau, W.Y. Bourinaris, T. Kaiyrzhanov, R. Chelban, V. Madej, M. Diana, M.C. Vari, M.S. Pedemonte, M. Bruno, C. Balagura, G. Scala, M. Fiorillo, C. Nobili, L. Malintan, N.T. Zanetti, M.N. Krishnakumar, S.S. Lignani, G. Jepson, J.E.C. Broda, P. Baldassari, S. Rossi, P. Fruscione, F. Madia, F. Traverso, M. De-Marco, P. Pérez-Dueñas, B. Munell, F. Kriouile, Y. El-Khorassani, M. Karashova, B. Avdjieva, D. Kathom, H. Tincheva, R. Van-Maldergem, L. Nachbauer, W. Boesch, S. Gagliano, A. Amadori, E. Goraya, J.S. Sultan, T. Kirmani, S. Ibrahim, S. Jan, F. Mine, J. Banu, S. Veggiotti, P. Zuccotti, G.V. Ferrari, M.D. Van Den Maagdenberg, A.M.J. Verrotti, A. Marseglia, G.L. Savasta, S. Soler, M.A. Scuderi, C. Borgione, E. Chimenz, R. Gitto, E. Dipasquale, V. Sallemi, A. Fusco, M. Cuppari, C. Cutrupi, M.C. Ruggieri, M. Cama, A. Capra, V. Mencacci, N.E. Boles, R. Gupta, N. Kabra, M. Papacostas, S. Zamba-Papanicolaou, E. Dardiotis, E. Maqbool, S. Rana, N. Atawneh, O. Lim, S.Y. Shaikh, F. Koutsis, G. Breza, M. Coviello, D.A. Dauvilliers, Y.A. AlKhawaja, I. AlKhawaja, M. Al-Mutairi, F. Stojkovic, T. Ferrucci, V. Zollo, M. Alkuraya, F.S. Kinali, M. Sherifa, H. Benrhouma, H. Turki, I.B.Y. Tazir, M. Obeid, M. Bakhtadze, S. Saadi, N.W. Zaki, M.S. Triki, C.C. Benfenati, F. Gustincich, S. Kara, M. Belcastro, V. Specchio, N. Capovilla, G. Karimiani, E.G. Salih, A.M. Okubadejo, N.U. Ojo, O.O. Oshinaike, O.O. Oguntunde, O. Wahab, K. Bello, A.H. Abubakar, S. Obiabo, Y. Nwazor, E. Ekenze, O. Williams, U. Iyagba, A. Taiwo, L. Komolafe, M. Senkevich, K. Shashkin, C. Zharkynbekova, N. Koneyev, K. Manizha, G. Isrofilov, M. Guliyeva, U. Salayev, K. Khachatryan, S. Rossi, S. Silvestri, G. Haridy, N. Ramenghi, L.A. Xiromerisiou, G. David, E. Aguennouz, M. Fidani, L. Spanaki, C. Tucci, A. Raspall-Chaure, M. Chez, M. Tsai, A. Fassi, E. Shinawi, M. Constantino, J.N. De Zorzi, R. Fortuna, S. Kok, F. Keren, B. Bonneau, D. Choi, M. Benzeev, B. Zara, F. Mefford, H.C. Scheffer, I.E. Clayton-Smith, J. Macaya, A. Rothman, J.E. Eichler, E.E. Kullmann, D.M. Houlden, H. SYNAPS Study Group

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. © 2019, The Author(s).

Published
2019

81. Prospective interest in deploying multi-omics approaches to solve unsolved patients with suspected monogenic developmental delay syndromes

Author

Duffourd, Y., Tisserant, E., Plagos, A., Callier, P., Tran-Them, F. Mau, Bruel, A., Denomme-Pichon, A., Philippe, C., Isidor, B., Heide, S., Afenjar, A., Rodriguez, D., Mignot, C., Heron, D., Vincent, M., Charles, P., Moutton, S., Jean, N., Odent, S., Dubourg, C., Faudet, A., Keren, B., Cogne, B., Boland, A., Olaso, R., Thauvin, C., Faivre, L., Deleuze, Jean-Francois, Vitobello, A., Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Equipe GAD (LNC - U1231), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Plateau technique de Biologie [CHU de Dijon], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), 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 ), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), 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), CHU Dijon, Jonchère, Laurent, Université de Rennes 1 (UR1), 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 ), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

82. The phenotypic spectrum of WWOX-related Epileptic Encephalopathy: 20 additional cases and review of the literature

Author

Piard, J., Hawkes, L., Milh, M., Villard, Laurent, Borgatti, R., Fradin, M., Capri, Y., Heron, D., Nougues, M., Nava, C., Arsene, O. Tarta, Shears, D., Sogawa, Y., Johnson, D., Firth, H., Vasudevan, P., Jones, G., Nguyen-Morel, M., Busa, T., Roubertie, A., Born, M., Koenig, M., Brischoux-Boucher, E., Mignot, C., Kini, U., Philippe, C., Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV.GEN]Life Sciences [q-bio]/Genetics
Abstract

51st Conference of the European-Society-of-Human-Genetics (ESHG) in conjunction with the European Meeting on Psychosocial Aspects of Genetics (EMPAG), Milan, ITALY, JUN 16-19, 2018; International audience

Published
2019

86. Fetal hypoxemia causes abnormal myocardial development in a preterm ex utero fetal ovine model

Author

William H. Peranteau, Heron D. Baumgarten, Avery C. Rossidis, Alan W. Flake, Ali Y. Mejaddam, Marcus G. Davey, Jack Rychik, Esha Bansal, Zhongshan Gou, Patrick E. McGovern, J. William Gaynor, Kendall M. Lawrence, Samson Hennessy-Strahs, Maryann Villeda, Carlo R. Bartoli, Jiancheng Han, and Sheng Zhao

Subjects
Cardiac function curve, Cardiac output, medicine.medical_specialty, Diastole, 030204 cardiovascular system & hematology, 03 medical and health sciences, Fetal Heart, Fetus, 0302 clinical medicine, Pregnancy, Internal medicine, Animals, Humans, Myocyte, Medicine, Hypoxia, Maternal-Fetal Exchange, reproductive and urinary physiology, Sheep, 030219 obstetrics & reproductive medicine, business.industry, Myocardium, Uterus, Infant, Newborn, General Medicine, Oxygenation, Hypoxia (medical), Oxygen, Disease Models, Animal, Fertility, Cardiovascular Diseases, In utero, embryonic structures, Cardiology, Female, medicine.symptom, business, Research Article
Abstract

In utero hypoxia is a major cause of neonatal morbidity and mortality and predisposes to adult cardiovascular disease. No therapies exist to correct fetal hypoxia. In a new ex utero fetal support system, we tested the hypothesis that hypoxemic support of the fetus impairs myocardial development, whereas normoxic support allows normal myocardial development. Preterm fetal lambs were connected via umbilical vessels to a low-resistance oxygenator and placed in a sterile-fluid environment. Control normoxic fetuses received normal fetal oxygenation, and hypoxemic fetuses received subphysiologic oxygenation. Fetuses with normal in utero development served as normal controls. Hypoxemic fetuses exhibited decreased maximum cardiac output in both ventricles, diastolic function, myocyte and myocyte nuclear size, and increased myocardial capillary density versus control normoxic fetuses. There were no differences between control normoxic fetuses in the fetal support system and normal in utero controls. Chronic fetal hypoxemia resulted in significant abnormalities in myocyte architecture and myocardial capillary density as well as systolic and diastolic cardiac function, whereas control fetuses showed no differences. This ex utero fetal support system has potential to become a significant research tool and novel therapy to correct fetal hypoxia.

Published
2018
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89. Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study

Author

Thauvin-Robinet, C., Cossee, M., Cormier-Daire, V., Van Maldergem, L., Toutain, A., Alembik, Y., Bieth, E., Layet, V., Parent, P., David, A., Goldenberg, A., Mortier, G., Heron, D., Sagot, P., Bouvier, A.M., Huet, F., Cusin, V., Donzel, A., Devys, D., Teyssier, J.R., and Faivre, L.

Subjects
Gene mutations -- Research, Genotype -- Analysis, Molecular genetics -- Research, Multiple abnormalities -- Development and progression, Multiple abnormalities -- Genetic aspects, Phenotype -- Analysis, X chromosome -- Analysis, X chromosome -- Physiological aspects, Health
Published
2006

91. De novo and biallelic DEAF1 variants cause a phenotypic spectrum

Author

Nabais Sá, MJ, Jensik, PJ, McGee, SR, Parker, MJ, Lahiri, N, McNeil, EP, Kroes, HY, Hagerman, RJ, Harrison, RE, Montgomery, T, Splitt, M, Palmer, EE, Sachdev, RK, Mefford, HC, Scott, AA, Martinez-Agosto, JA, Lorenz, R, Orenstein, N, Berg, JN, Amiel, J, Heron, D, Keren, B, Cobben, JM, Menke, LA, Marco, EJ, Graham, JM, Pierson, TM, Karimiani, EG, Maroofian, R, Manzini, MC, Cauley, ES, Colombo, R, Odent, S, Dubourg, C, Phornphutkul, C, de Brouwer, APM, de Vries, BBA, Vulto-vanSilfhout, AT, Nabais Sá, MJ, Jensik, PJ, McGee, SR, Parker, MJ, Lahiri, N, McNeil, EP, Kroes, HY, Hagerman, RJ, Harrison, RE, Montgomery, T, Splitt, M, Palmer, EE, Sachdev, RK, Mefford, HC, Scott, AA, Martinez-Agosto, JA, Lorenz, R, Orenstein, N, Berg, JN, Amiel, J, Heron, D, Keren, B, Cobben, JM, Menke, LA, Marco, EJ, Graham, JM, Pierson, TM, Karimiani, EG, Maroofian, R, Manzini, MC, Cauley, ES, Colombo, R, Odent, S, Dubourg, C, Phornphutkul, C, de Brouwer, APM, de Vries, BBA, and Vulto-vanSilfhout, AT

Abstract

Purpose: To investigate the effect of different DEAF1 variants on the phenotype of patients with autosomal dominant and recessive inheritance patterns and on DEAF1 activity in vitro. Methods: We assembled a cohort of 23 patients with de novo and biallelic DEAF1 variants, described the genotype–phenotype correlation, and investigated the differential effect of de novo and recessive variants on transcription assays using DEAF1 and Eif4g3 promoter luciferase constructs. Results: The proportion of the most prevalent phenotypic features, including intellectual disability, speech delay, motor delay, autism, sleep disturbances, and a high pain threshold, were not significantly different in patients with biallelic and pathogenic de novo DEAF1 variants. However, microcephaly was exclusively observed in patients with recessive variants (p < 0.0001). Conclusion: We propose that different variants in the DEAF1 gene result in a phenotypic spectrum centered around neurodevelopmental delay. While a pathogenic de novo dominant variant would also incapacitate the product of the wild-type allele and result in a dominant-negative effect, a combination of two recessive variants would result in a partial loss of function. Because the clinical picture can be nonspecific, detailed phenotype information, segregation, and functional analysis are fundamental to determine the pathogenicity of novel variants and to improve the care of these patients.

Published
2019

92. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

Author

O'Donnell-Luria, A.H., Pais, L.S., Faundes, V., Wood, J.C., Sveden, A., Luria, V., Jamra, R. Abou, Accogli, A., Amburgey, K., Anderlid, B.M., Azzarello-Burri, S., Basinger, A.A., Bianchini, C., Bird, L.M., Buchert, R., Carre, W., Ceulemans, S., Charles, P., Cox, H., Culliton, L., Curro, A., Demurger, F., Dowling, J.J., Duban-Bedu, B., Dubourg, C., Eiset, S.E., Escobar, L.F., Ferrarini, A., Haack, T.B., Hashim, M., Heide, S. van der, Helbig, K.L., Helbig, I., Heredia, R., Heron, D., Isidor, B., Jonasson, A.R., Joset, P., Keren, B., Kok, F., Kroes, H.Y., Lavillaureix, A., Lu, X., Maas, S.M., Maegawa, G.H., Marcelis, C.L.M., Mark, P.R., Masruha, M.R., McLaughlin, H.M., McWalter, K., Melchinger, E.U., Mercimek-Andrews, S., Nava, C., Pendziwiat, M., Person, R., Ramelli, G.P., Ramos, L.L.P., Rauch, A., Reavey, C., Renieri, A., Riess, A., Sanchez-Valle, A., Sattar, S., Saunders, C., Schwarz, N., Smol, T., Srour, M., Steindl, K., Syrbe, S., Taylor, J.C., Telegrafi, A., Thiffault, I., Trauner, D.A., Linden, H., Jr. van der, Koningsbruggen, S. van, Villard, L., Vogel, I., Vogt, J., Weber, Y.G., Wentzensen, I.M., Widjaja, E., Zak, J., Baxter, S., Banka, S., Rodan, L.H., O'Donnell-Luria, A.H., Pais, L.S., Faundes, V., Wood, J.C., Sveden, A., Luria, V., Jamra, R. Abou, Accogli, A., Amburgey, K., Anderlid, B.M., Azzarello-Burri, S., Basinger, A.A., Bianchini, C., Bird, L.M., Buchert, R., Carre, W., Ceulemans, S., Charles, P., Cox, H., Culliton, L., Curro, A., Demurger, F., Dowling, J.J., Duban-Bedu, B., Dubourg, C., Eiset, S.E., Escobar, L.F., Ferrarini, A., Haack, T.B., Hashim, M., Heide, S. van der, Helbig, K.L., Helbig, I., Heredia, R., Heron, D., Isidor, B., Jonasson, A.R., Joset, P., Keren, B., Kok, F., Kroes, H.Y., Lavillaureix, A., Lu, X., Maas, S.M., Maegawa, G.H., Marcelis, C.L.M., Mark, P.R., Masruha, M.R., McLaughlin, H.M., McWalter, K., Melchinger, E.U., Mercimek-Andrews, S., Nava, C., Pendziwiat, M., Person, R., Ramelli, G.P., Ramos, L.L.P., Rauch, A., Reavey, C., Renieri, A., Riess, A., Sanchez-Valle, A., Sattar, S., Saunders, C., Schwarz, N., Smol, T., Srour, M., Steindl, K., Syrbe, S., Taylor, J.C., Telegrafi, A., Thiffault, I., Trauner, D.A., Linden, H., Jr. van der, Koningsbruggen, S. van, Villard, L., Vogel, I., Vogt, J., Weber, Y.G., Wentzensen, I.M., Widjaja, E., Zak, J., Baxter, S., Banka, S., and Rodan, L.H.

Abstract

Contains fulltext : 206572.pdf (publisher's version ) (Open Access), We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.

Published
2019

93. The glacier-influenced marine record on high-latitude continental margins: synergies between modern, Quaternary and ancient evidence

Author

Dowdeswell, J.A., Hogan, Kelly A., Le Heron, D. P., Dowdeswell, J.A., Hogan, Kelly A., and Le Heron, D. P.

Abstract

Major glaciations or ‘ice ages’ are known to have affected the Earth's surface over the past three billion years. The best preserved records of these glaciations are often found in high-latitude continental margin settings where sediment has been delivered to, and then accumulated at, the edge of the ice sheet in thick glacier-influenced marine sequences. The composition and geometry of these deposits and the related assemblages of glacial landforms provide a wealth of information about the environmental setting during successive cycles of glaciation and deglaciation, including ice-dynamic and oceanographic processes. Here, we discuss modern (present day), Quaternary (last 2.6 myr) and ancient (last 1 gyr) high-latitude continental margin settings, and then contrast the methodologies used and glacier-influenced deposits and landforms most often identified for each time period. We use examples from the literature to identify synergies, as well as to note differences, between studies of glacier-influenced sediments from ancient to modern environments.

Published
2019

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

Author

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, Mannikko, 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, J-H, 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-Penas, J, Carracedo, A, Van Haeringen, A, Ruivenkamp, C, Nava, C, Heron, D, Nardello, R, Iacomino, M, Minetti, C, Skabar, A, Fabretto, A, 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, Raspall-Chaure, M, Hanna, MG, Bugiardini, E, Hostettler, I, O'Callaghan, B, Khan, A, Cortese, A, O'Connor, E, Yau, WY, Bourinaris, T, Kaiyrzhanov, R, Chelban, V, Madej, M, Diana, MC, Vari, MS, Pedemonte, M, Bruno, C, Balagura, G, Scala, M, Fiorillo, C, Nobili, L, Malintan, NT, Zanetti, MN, Krishnakumar, SS, Lignani, G, Jepson, JEC, Broda, P, Baldassari, S, Rossi, P, Fruscione, F, Madia, F, Traverso, M, De-Marco, P, Perez-Duenas, B, Munell, F, Kriouile, Y, El-Khorassani, M, Karashova, B, Avdjieva, D, Kathom, H, Tincheva, R, Van-Maldergem, L, Nachbauer, W, Boesch, S, Gagliano, A, Amadori, E, Goraya, JS, Sultan, T, Kirmani, S, Ibrahim, S, Jan, F, Mine, J, Banu, S, Veggiotti, P, Zuccotti, G, Ferrari, MD, Van Den Maagdenberg, AMJ, Verrotti, A, Marseglia, GL, Savasta, S, Soler, MA, Scuderi, C, Borgione, E, Chimenz, R, Gitto, E, Dipasquale, V, Sallemi, A, Fusco, M, Cuppari, C, Cutrupi, MC, Ruggieri, M, Cama, A, Capra, V, Mencacci, NE, Boles, R, Gupta, N, Kabra, M, Papacostas, S, Zamba-Papanicolaou, E, Dardiotis, E, Maqbool, S, Rana, N, Atawneh, O, Lim, SY, Shaikh, F, Koutsis, G, Breza, M, Coviello, DA, Dauvilliers, YA, AlKhawaja, I, AlKhawaja, M, Al-Mutairi, F, Stojkovic, T, Ferrucci, V, Zollo, M, Alkuraya, FS, Kinali, M, Sherifa, H, Benrhouma, H, Turki, IBY, Tazir, M, Obeid, M, Bakhtadze, S, Saadi, NW, Zaki, MS, Triki, CC, Benfenati, F, Gustincich, S, Kara, M, Belcastro, V, Specchio, N, Capovilla, G, Karimiani, EG, Salih, AM, Okubadejo, NU, Ojo, OO, Oshinaike, OO, Oguntunde, O, Wahab, K, Bello, AH, Abubakar, S, Obiabo, Y, Nwazor, E, Ekenze, O, Williams, U, Iyagba, A, Taiwo, L, Komolafe, M, Senkevich, K, Shashkin, C, Zharkynbekova, N, Koneyev, K, Manizha, G, Isrofilov, M, Guliyeva, U, Salayev, K, Khachatryan, S, Rossi, S, Silvestri, G, Haridy, N, Ramenghi, LA, Xiromerisiou, G, David, E, Aguennouz, M, Fidani, L, Spanaki, C, Tucci, A, 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, Mannikko, 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, J-H, 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-Penas, J, Carracedo, A, Van Haeringen, A, Ruivenkamp, C, Nava, C, Heron, D, Nardello, R, Iacomino, M, Minetti, C, Skabar, A, Fabretto, A, 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, Raspall-Chaure, M, Hanna, MG, Bugiardini, E, Hostettler, I, O'Callaghan, B, Khan, A, Cortese, A, O'Connor, E, Yau, WY, Bourinaris, T, Kaiyrzhanov, R, Chelban, V, Madej, M, Diana, MC, Vari, MS, Pedemonte, M, Bruno, C, Balagura, G, Scala, M, Fiorillo, C, Nobili, L, Malintan, NT, Zanetti, MN, Krishnakumar, SS, Lignani, G, Jepson, JEC, Broda, P, Baldassari, S, Rossi, P, Fruscione, F, Madia, F, Traverso, M, De-Marco, P, Perez-Duenas, B, Munell, F, Kriouile, Y, El-Khorassani, M, Karashova, B, Avdjieva, D, Kathom, H, Tincheva, R, Van-Maldergem, L, Nachbauer, W, Boesch, S, Gagliano, A, Amadori, E, Goraya, JS, Sultan, T, Kirmani, S, Ibrahim, S, Jan, F, Mine, J, Banu, S, Veggiotti, P, Zuccotti, G, Ferrari, MD, Van Den Maagdenberg, AMJ, Verrotti, A, Marseglia, GL, Savasta, S, Soler, MA, Scuderi, C, Borgione, E, Chimenz, R, Gitto, E, Dipasquale, V, Sallemi, A, Fusco, M, Cuppari, C, Cutrupi, MC, Ruggieri, M, Cama, A, Capra, V, Mencacci, NE, Boles, R, Gupta, N, Kabra, M, Papacostas, S, Zamba-Papanicolaou, E, Dardiotis, E, Maqbool, S, Rana, N, Atawneh, O, Lim, SY, Shaikh, F, Koutsis, G, Breza, M, Coviello, DA, Dauvilliers, YA, AlKhawaja, I, AlKhawaja, M, Al-Mutairi, F, Stojkovic, T, Ferrucci, V, Zollo, M, Alkuraya, FS, Kinali, M, Sherifa, H, Benrhouma, H, Turki, IBY, Tazir, M, Obeid, M, Bakhtadze, S, Saadi, NW, Zaki, MS, Triki, CC, Benfenati, F, Gustincich, S, Kara, M, Belcastro, V, Specchio, N, Capovilla, G, Karimiani, EG, Salih, AM, Okubadejo, NU, Ojo, OO, Oshinaike, OO, Oguntunde, O, Wahab, K, Bello, AH, Abubakar, S, Obiabo, Y, Nwazor, E, Ekenze, O, Williams, U, Iyagba, A, Taiwo, L, Komolafe, M, Senkevich, K, Shashkin, C, Zharkynbekova, N, Koneyev, K, Manizha, G, Isrofilov, M, Guliyeva, U, Salayev, K, Khachatryan, S, Rossi, S, Silvestri, G, Haridy, N, Ramenghi, LA, Xiromerisiou, G, David, E, Aguennouz, M, Fidani, L, Spanaki, C, and Tucci, A

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.

Published
2019

95. SLC35A2-CDG: Functional characterization, expanded molecular, clinical, and biochemical phenotypes of 30 unreported Individuals

Author

Ng, BG, Sosicka, P, Agadi, S, Almannai, M, Bacino, CA, Barone, R, Botto, LD, Burton, JE, Carlston, C, Chung, BH-Y, Cohen, JS, Coman, D, Dipple, KM, Dorrani, N, Dobyns, WB, Elias, AF, Epstein, L, Gahl, WA, Garozzo, D, Hammer, TB, Haven, J, Heron, D, Herzog, M, Hoganson, GE, Hunter, JM, Jain, M, Juusola, J, Lakhani, S, Lee, H, Lee, J, Lewis, K, Longo, N, Lourenco, CM, Mak, CCY, McKnight, D, Mendelsohn, BA, Mignot, C, Mirzaa, G, Mitchell, W, Muhle, H, Nelson, SF, Olczak, M, Palmer, CGS, Partikian, A, Patterson, MC, Pierson, TM, Quinonez, SC, Regan, BM, Ross, ME, Guillen Sacoto, MJ, Scaglia, F, Scheffer, IE, Segal, D, Singhal, NS, Striano, P, Sturiale, L, Symonds, JD, Tang, S, Vilain, E, Willis, M, Wolfe, LA, Yang, H, Yano, S, Powis, Z, Suchy, SF, Rosenfeld, JA, Edmondson, AC, Grunewald, S, Freeze, HH, Ng, BG, Sosicka, P, Agadi, S, Almannai, M, Bacino, CA, Barone, R, Botto, LD, Burton, JE, Carlston, C, Chung, BH-Y, Cohen, JS, Coman, D, Dipple, KM, Dorrani, N, Dobyns, WB, Elias, AF, Epstein, L, Gahl, WA, Garozzo, D, Hammer, TB, Haven, J, Heron, D, Herzog, M, Hoganson, GE, Hunter, JM, Jain, M, Juusola, J, Lakhani, S, Lee, H, Lee, J, Lewis, K, Longo, N, Lourenco, CM, Mak, CCY, McKnight, D, Mendelsohn, BA, Mignot, C, Mirzaa, G, Mitchell, W, Muhle, H, Nelson, SF, Olczak, M, Palmer, CGS, Partikian, A, Patterson, MC, Pierson, TM, Quinonez, SC, Regan, BM, Ross, ME, Guillen Sacoto, MJ, Scaglia, F, Scheffer, IE, Segal, D, Singhal, NS, Striano, P, Sturiale, L, Symonds, JD, Tang, S, Vilain, E, Willis, M, Wolfe, LA, Yang, H, Yano, S, Powis, Z, Suchy, SF, Rosenfeld, JA, Edmondson, AC, Grunewald, S, and Freeze, HH

Abstract

Pathogenic de novo variants in the X-linked gene SLC35A2 encoding the major Golgi-localized UDP-galactose transporter required for proper protein and lipid glycosylation cause a rare type of congenital disorder of glycosylation known as SLC35A2-congenital disorders of glycosylation (CDG; formerly CDG-IIm). To date, 29 unique de novo variants from 32 unrelated individuals have been described in the literature. The majority of affected individuals are primarily characterized by varying degrees of neurological impairments with or without skeletal abnormalities. Surprisingly, most affected individuals do not show abnormalities in serum transferrin N-glycosylation, a common biomarker for most types of CDG. Here we present data characterizing 30 individuals and add 26 new variants, the single largest study involving SLC35A2-CDG. The great majority of these individuals had normal transferrin glycosylation. In addition, expanding the molecular and clinical spectrum of this rare disorder, we developed a robust and reliable biochemical assay to assess SLC35A2-dependent UDP-galactose transport activity in primary fibroblasts. Finally, we show that transport activity is directly correlated to the ratio of wild-type to mutant alleles in fibroblasts from affected individuals.

Published
2019

96. The phenotypic spectrum of WWOX-related disorders: 20 additional cases of WOREE syndrome and review of the literature

Author

Piard, J, Hawkes, L, Milh, M, Villard, L, Borgatti, R, Romaniello, R, Fradin, M, Capri, Y, Heron, D, Nougues, MC, Nava, C, Arsene, OT, Shears, D, Taylor, J, Pagnamenta, A, Taylor, JC, Sogawa, Y, Johnson, D, Firth, H, Vasudevan, P, Jones, G, Nguyen-Morel, MA, Busa, T, Roubertie, A, van den Born, Myrthe, Brischoux-Boucher, E, Koenig, M, Mignot, C, Kini, U, Philippe, C, Piard, J, Hawkes, L, Milh, M, Villard, L, Borgatti, R, Romaniello, R, Fradin, M, Capri, Y, Heron, D, Nougues, MC, Nava, C, Arsene, OT, Shears, D, Taylor, J, Pagnamenta, A, Taylor, JC, Sogawa, Y, Johnson, D, Firth, H, Vasudevan, P, Jones, G, Nguyen-Morel, MA, Busa, T, Roubertie, A, van den Born, Myrthe, Brischoux-Boucher, E, Koenig, M, Mignot, C, Kini, U, and Philippe, C

Published
2019

97. Myhre syndrome: new reports, review, and differential diagnosis. (Letters to JMG)

Author

Burglen, L., Heron, D., Moerman, A., Dieux-Coeslier, A., Bourguignon, J-P, Bachy, A., Carel, J-C, Cormier-Daire, V., Manouvrier, S., and Verloes, A.

Subjects
Genetic disorders -- Diagnosis, Genetic research, Genetic screening, Health, Diagnosis
Abstract

Several conditions characterised by short fingers, reduced joint mobility, short stature, and muscular build with or without mental retardation have been delineated during the past 30 years: Moore-Federman syndrome, Myhre [...]

Published
2003

98. Genetic testing and genetic counselling in hypertrophic cardiomyopathy: the French experience. (Medical Genetics in Practice)

Author

Charron, P., Heron, D., Gargiulo, M., Richard, P., Dubourg, O., Desnos, M., Bouhour, J-B, Feingold, J., Carrier, L., Hainque, B., Schwartz, K., and Komajda, M.

Subjects
Gene mutations -- Health aspects -- Usage -- Social aspects -- Research -- Physiological aspects -- Genetic aspects -- Psychological aspects, Familial diseases -- Research -- Genetic aspects, Molecular genetics -- Research -- Genetic aspects -- Social aspects -- Psychological aspects -- Physiological aspects -- Health aspects -- Usage, Cardiomyopathy, Hypertrophic -- Psychological aspects -- Genetic aspects -- Research, Genetic counseling -- Usage -- Psychological aspects -- Research -- Physiological aspects -- Social aspects -- Health aspects, Sudden death -- Causes of -- Genetic aspects -- Research, Medical genetics -- Research -- Health aspects -- Physiological aspects -- Usage -- Social aspects -- Psychological aspects, Children -- Physiological aspects -- Social aspects -- Genetic aspects -- Psychological aspects -- Health aspects -- Research -- Usage, Amniocentesis -- Usage -- Health aspects -- Research -- Physiological aspects -- Psychological aspects -- Social aspects, Genetic screening -- Standards -- Usage -- Genetic aspects -- Physiological aspects -- Research -- Health aspects -- Social aspects -- Psychological aspects, Health, Psychological aspects, Standards, Social aspects, Physiological aspects, Usage, Research, Genetic aspects, Health aspects, Causes of
Abstract

Aims: A major breakthrough in the molecular genetics of hypertrophic cardiomyopathy (HCM) has made genetic testing now available in clinical practice, raising new questions about its implications, potential benefits, and [...]

Published
2002

99. First occurrence of bidens mottle virus in Brazil: biological and molecular characterization of isolates infecting Zinnia sp. and Bidens pilosa

Author

Gabriel Madoglio Favara, Camila Geovana Ferro, Vinicius Henrique Bello, Felipe Franco de Oliveira, Heron Delgado Kraide, Marcos Roberto Ribeiro Junior, Renate Krause-Sakate, Elliot Watanabe Kitajima, and Jorge Alberto Marques Rezende

Subjects
BiMoV, Potyvirus, high-throughput sequencing, Agriculture (General), S1-972
Abstract

ABSTRACT Zinnia sp. and hairy beggartick (Bidens pilosa) plants exhibiting symptoms of possible virus infection were found in the municipality of Santa Bárbara d’Oeste, São Paulo State, Brazil. Flexuous filamentous particles and cytoplasmatic inclusions typical of potyvirus infection were observed by transmission electron microscopy, respectively, in leaf extracts and cells of symptomatic leaves. Infection of both plants with bidens mottle virus (BiMoV) was confirmed by RT-PCR using potyvirus universal primers, followed by nucleotide sequencing of the amplicons. The nearly complete genome sequence of the Brazilian isolate, named BiMoV-BR, is 9700 nucleotides long and shares 95.6 % identity with the corresponding nucleotide sequence of a BiMoV isolate from the United States. BiMoV-BR was mechanically transmitted and caused systemic infection on plants of Zinnia sp., hairy beggarstick, sunflower (Helianthus annuus), and lettuce (Lactuca sativa). Myzus persicae transmitted the virus to Zinnia sp. plants with efficacy of 8 % and 42 %, using one and ten aphids per plant, respectively. This is the first detection of BiMoV in Brazil. Further studies are necessary to evaluate the distribution of this potyvirus in the country.

Published
2023
Full Text
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100. Laparoscopic appendectomy - Outcomes of senior trainees operating without supervision versus experienced pediatric surgeons

Author

Heron D. Baumgarten, Erin G. Brown, N. Scott Adzick, Pablo Laje, and Kathryn W. Russell

Subjects
Reoperation, medicine.medical_specialty, Adolescent, Operative Time, Patient Readmission, Pediatrics, Specialties, Surgical, 03 medical and health sciences, Young Adult, 0302 clinical medicine, 030225 pediatrics, Pediatric surgery, medicine, Appendectomy, Humans, Major complication, Child, Intraoperative Complications, Fellowship training, Retrospective Studies, Perforated Appendicitis, business.industry, General surgery, Pediatric Surgeon, General Medicine, Length of Stay, Appendicitis, 030220 oncology & carcinogenesis, Child, Preschool, Pediatrics, Perinatology and Child Health, Operative time, Surgery, Laparoscopy, Clinical Competence, business, Hospital stay
Abstract

Aim of the study Pediatric surgery trainees at our program are allowed to perform unsupervised laparoscopic appendectomies during their last year of training to promote independent operative decision-making skills. We reviewed the outcomes of laparoscopic appendectomies done by senior trainees without supervision and compared them to experienced pediatric surgeons. Methods We reviewed 500 laparoscopic appendectomies performed without supervision by the last 10 pediatric surgery trainees during their last year of training (first 50 cases of each trainee). We compared the outcomes of those 500 cases to the outcomes of 200 laparoscopic appendectomies performed by eight experienced pediatric surgeons (last 25 cases of each surgeon). Data are expressed as mean (SD), unless otherwise indicated. A P value of ≤ 0.05 was regarded as significant. Main results Median age in the “trainees” and “surgeons” groups was 11 (range 2–22) and 12 (2–20) years, respectively (P = 0.35). The proportion of perforated appendicitis was similar: 98/500 (19.6%) in the trainees group and 42/200 (21%) in the surgeons group, respectively (P = 0.75). Mean operative time was 41 (SD 14.5) min in the trainees group vs. 39 (SD 16.1) min in the surgeons group (P = 0.05). Minor intraoperative complications occurred in 3/500 (0.6%) cases in the trainees group vs. 1/200 (0.5%) in the surgeons group (P = 0.69). No major complications occurred in either group. Mean hospital stay was 2 (range 0.5–26) and 2.3 (range 0.5–18) days in the trainees and surgeons groups, respectively (P = 0.25). There were 13/500 vs. 5/200 readmissions (P = 0.92), and 1/500 vs. 1/200 reoperations in the trainees and surgeons groups, respectively (P = 0.91). Conclusion Allowing senior pediatric surgery trainees to perform laparoscopic appendectomies without supervision to stimulate surgical autonomy is safe and does not compromise patient outcomes. Level of evidence III.

Published
2018

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