Case report: A novel mosaic nonsense mutation of PCDH19 in a Chinese male with febrile epilepsy

Abstract

The clinical features of the PCDH19 gene mutation include febrile epilepsy ranging from mild to severe, with or without intellectual disability, cognitive impairment, and psych-behavioral disorders, but there has been little research on males with the mosaic mutation of PCDH19. This study reported a novel, de novo, and mosaic PCDH19 nonsense mutation (NM_001184880: c.840C > A, p. Tyr280*) from a Chinese male in early middle childhood by trio whole-exome sequence (Trio-WES) and confirmed by Sanger sequence. The proportion of the mosaic mutation (c.840C > A, p. Tyr280*) in PCDH19 was 27.9% in, buccal mucosal cells, 48.3% in exfoliated cells in the urine, and 50.6% in peripheral blood of proband. He had the first onset of seizures in toddlerhood with febrile epilepsy, mild impaired cognitive psychological, and behavioral abnormalities. The electroencephalography (EEG) exhibited sharp waves and sharp slow complex waves in the bilateral parietal, occipital, and posterior temporal regions during the interictal period. Pinpoint white matter lesions in the periventricular white matter and slightly bulging bilateral ventricles appeared on cranial magnetic resonance imaging (MRI). With Depakine and Keppra he gained good control over his epilepsy. This study might expand the genotypes and broaden the spectrums.

In vitro human cell culture models in a bench‐to‐bedside approach to epilepsy

“…The most accessible method for studying genetic epilepsies using patient‐derived human cells is the employment of somatic nonneural cells (e.g. dermal fibroblasts, peripheral blood cells, buccal cells, exfoliated cells in the urine, and other cell types 74 , 75 , 76 ). Even though of nonneural origin, these cells are commonly utilized for detecting pathogenic variants of epilepsy‐related genes 77 , 78 , 79 , 80 and as source cells for reprogramming into iPSCs.…”