Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders
| Autor: | Willem F. M. Arts, Dick Lindhout, P. De Jonghe, Katia Hardies, J. F. de Rijk-van Andel, Eva H. Brilstra, András Fogarasi, J. J. T. van Harssel, M. V. de Jonge, Anna Jansen, W. B. Gunning, Arvid Suls, Nienke E. Verbeek, M.J.A. van Kempen, E. van Daalen, Helene Verhelst, R. Vermeulen, Sarah Weckhuysen, Anna Kelemen, C. G. F. de Kovel, Bobby P. C. Koeleman |
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| Přispěvatelé: | Public Health Care, Neurogenetics, Child and Adolescent Psychiatry / Psychology, Internal Medicine, Public Health, Neurology, Clinical Genetics, Pediatric surgery, NCA - Brain mechanisms in health and disease |
| Rok vydání: | 2012 |
| Předmět: |
Proband
Male Pediatrics medicine.medical_specialty Adolescent Epilepsies Myoclonic Penetrance Cohort Studies Cellular and Molecular Neuroscience Epilepsy Dravet syndrome Intellectual Disability medicine Missense mutation Humans genetics Genetic Predisposition to Disease Autism spectrum disorder Child Biology Genetics (clinical) Genetic Association Studies Genetics X-linked Sex Characteristics business.industry Syndrome medicine.disease Cadherins Protocadherins Child Development Disorders Pervasive Child Preschool Epilepsy syndromes Mutation Autism Female Human medicine business |
| Zdroj: | van Harssel, J J T, Weckhuysen, S, van Kempen, M J A, Hardies, K, Verbeek, N E, de Kovel, C G F, Gunning, W B, van Daalen, E, de Jonge, M V, Jansen, A C, Vermeulen, R J, Arts, W F M, Verhelst, H, Fogarasi, A, de Rijk-van Andel, J, Kelemen, A, Lindhout, D, De Jonghe, P, Koeleman, B P C, Suls, A & Brilstra, E H 2013, ' Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders ', Neurogenetics, vol. 14, no. 1, pp. 23-34 . https://doi.org/10.1007/s10048-013-0353-1 Vrije Universiteit Brussel Neurogenetics, 14(1), 23-34. Springer-Verlag Neurogenetics Neurogenetics, 14(1), 23-34. Springer Verlag |
| ISSN: | 1364-6753 1364-6745 |
| DOI: | 10.1007/s10048-013-0353-1 |
| Popis: | Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations. |
| Databáze: | OpenAIRE |
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