Genetic Mutation and Phenotype Analysis in A Five-Generation Chinese Pedigree with PCDH19 Female-Limited Epilepsy (PCDH19-FE)

Objective: PCDH19 female-limited epilepsy (PCDH19-FE) is an epileptic syndrome characterized by early-onset, clusters of febrile or afebrile seizures, and neuropsychiatric disorders. Located at Xq22.1, PCDH19 encodes one of the cell adhesion molecules, protocadherin 19. While the pathogenic gene is ascertained, the genotype-phenotype heterogeneity of PCDH19-FE is strong, and the mechanism of this heterogeneity remains obscure.Methods: We analyze the clinical data and genetic variants of a PCDH19-FE pedigree, to explore the heterogeneity of PCDH19-FE and underlying mechanisms. In addition to clinical information about the family members, second-generation sequencing and multiplex ligation-dependent probe amplification (MLPA) were adopted to detect the mutation sites of probands with validation by sanger sequencing. The biological conservation analysis of the corresponding gene mutations and population polymorphism analysis were also performed subsequently. And a sanger sequencing was conducted in other patients in this pedigree. Furthermore, the X-inactivation mode was detected by methylation-sensitive restriction enzyme digestion product amplification and capillary electrophoresis.