The PCDH19 gene has been associated with X-linked epilepsy in the past. Variants in PCDH19 have been reported in humans as early as 2008. Initially, the phenotypic description was that of intellectual disability and seizures with onset in the later part of infancy affecting girls. Subsequently, a broader spectrum of epilepsy phenotypes has emerged, including affected mosaic males. At least 11 variants (missense and de novo) were curated from two publications (19214208, 21480887). While there is no experimental support directly linking the gene to epilepsy, there is reasonable biological plausibility and the mechanism of the unusual sparing of the hemizygous condition has robust experimental support. In summary, there is definitive evidence to support this gene-disease association, replicated over more than a decade at the time of this curation. The Epilepsy Gene Curation Expert Panel has decided to curate this gene for X-linked complex neurodevelopmental disorder (Mondo:0100038) because of the presence of ID/DD and epilepsy. This classification was approved by the ClinGen Epilepsy Gene Curation Expert Panel on 9/4/18 (SOP Version 6).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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