1. Male patients affected by mosaic PCDH19 mutations: five new cases
- Author
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Grazia M.S. Mancini, Cacha M.P.C.D. Peeters-Scholte, Paul B. Augustijn, Dick Lindhout, Eva H. Brilstra, A I Kistemaker, M.J.A. van Kempen, H A Newman, Oebele F. Brouwer, Katherine L. Helbig, Rinze F. Neuteboom, Marjolein Kriek, Bobby P. C. Koeleman, Patrick Rump, Yvonne J. Vos, I M de Lange, K. Hodges, Nine V A M Knoers, Neurology, and Clinical Genetics
- Subjects
0301 basic medicine ,Male ,DISORDER ,Pediatrics ,PCDH19 ,Intellectual disability ,Disease ,DE-NOVO ,Epilepsy ,0302 clinical medicine ,Genetics (clinical) ,Genetics ,PCDH19-RELATED EPILEPSY ,medicine.diagnostic_test ,Mosaicism ,Medical record ,High-Throughput Nucleotide Sequencing ,ENCEPHALOPATHY ,Cadherins ,Phenotype ,PROTOCADHERIN 19 MUTATIONS ,Female ,Original Article ,medicine.medical_specialty ,Heterozygote ,Encephalopathy ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Sex Factors ,Seizures ,medicine ,Journal Article ,Humans ,Genetic Predisposition to Disease ,Genetic testing ,SPECTRUM ,business.industry ,GENE-RELATED EPILEPSY ,medicine.disease ,FEMALE-LIMITED EPILEPSY ,Human genetics ,Protocadherins ,030104 developmental biology ,Mutation ,business ,030217 neurology & neurosurgery ,MENTAL-RETARDATION - Abstract
Pathogenic variants in the PCDH19 gene are associated with epilepsy, intellectual disability (ID) and behavioural disturbances. Only heterozygous females and mosaic males are affected, likely due to a disease mechanism named cellular interference. Until now, only four affected mosaic male patients have been described in literature. Here, we report five additional male patients, of which four are older than the oldest patient reported so far. All reported patients were selected for genetic testing because of developmental delay and/or epilepsy. Custom-targeted next generation sequencing gene panels for epilepsy genes were used. Clinical data were collected from medical records. All patients were mosaic in blood for likely pathogenic variants in the PCDH19 gene. In most, clinical features were very similar to the female phenotype, with normal development before seizure onset, which occurred between 5 and 10 months of age, clustering of seizures and sensitivity to fever. Four out of five patients had mild to severe ID and behavioural problems. We reaffirm the similarity between male and female PCDH19-related phenotypes, now also in a later phase of the disorder (ages 10–14 years). Electronic supplementary material The online version of this article (doi:10.1007/s10048-017-0517-5) contains supplementary material, which is available to authorized users.
- Published
- 2017