Abstract
BACKGROUND: Epilepsy limited to females with mental retardation (EFMR) is a rare type of epilepsy with an X-linked mode of inheritance, which affect heterozygous females while the males are not affected. Mutations within the protocadherin 19 (PCDH19) gene have been identified as the direct cause of EFMR. The phenotype of EFMR is characterized by seizure onset in infancy with or without cognitive impairment, intellectual disturbances, and autistic features. METHODS: Whole-exome sequencing (WES) was performed in the proband to identify the underlying genetic mutations. The candidate genes were confirmed by Sanger sequencing following PCR amplification. In silico analyses were conducted to predict the effect of the novel missense mutation on the function of PCDH19 protein. RESULTS: We identified three female patients in a family with a novel missense mutation in PCDH19, c.812G>A (p. (Gly271Asp)). The patients III-1 and III-2 presented with more severe clinical phenotypes and an earlier age of onset (6 and 11 months, respectively), intellectual disability, and movement disorders. By contrast, patient II-4 has a later age of onset (23 months), and there was no relapse of seizures without antiepileptic treatment after the age of six. In silico analyses showed that p. (Gly271Asp) in the PCDH19 affects a highly conserved residue. CONCLUSIONS: Our results indicated that patients with the same PCDH19 mutation in a family may show intrafamilial phenotypic variability. Givening the mother of the proband was 18 weeks pregnant and intends to have a prenatal diagnosis, the more reasonable and less harmful strategies for prenatal diagnosis could be chosen based on the results of noninvasive prenatal testing and genetic testing.