Identification of a pathogenic mutation in PCDH19-related female-limited epilepsy

Abstract Background Early infantile epilepticencephalopathy-9 (EIEE9) is an X-linked genetic disorder characterized by the onset of seizures during infancy. Mutations in PCDH19 are the main causes of EIEE9. The subject of our study is a child who presented with recurrent epileptic seizures and findings of abnormal synchronous discharges on electroencephalography. Our study aimed to identify causative variants of pathogenic genes and to confirm the diagnosis of epilepsy. Case presentation The proband is a girl who had been experiencing recurrent epileptic seizures for more than 2 years. The electroencephalography features strongly supported the diagnosis of epileptic encephalopathy. Whole-exome sequencing (WES) was conducted on the proband and parents to identify potential genetic variants. Candidate pathogenic variants were validated using Sanger sequencing. A pathogenic heterozygous variant was observed in PCDH19 (c.695A > G). Two likely benign variants, c.71C > T in GABRD and c.G1691A in SCN1A were also identified, including a paternally inherited nonsense heterozygous variant. Conclusions Based on clinical phenotyping and genetic analyses, the patient was diagnosed with PCDH19-female limited epilepsy. The application of WES to reveal the pathogenic variant was a crucial step in arriving at an accurate diagnosis. Genetic testing improves the diagnoses of PCDH19-related epilepsy manifesting with typical symptoms and provides valuable evidence that may enhance genetic counseling and clinical treatment guidance.