A case of early‐onset epileptic encephalopathy with a homozygous TBC1D24 variant caused by uniparental isodisomy

TBC1D24‐related disorders are rare neurodevelopmental disorders that show a broad range of neuropsychiatric deficits and are mostly inherited in an autosomal recessive manner. Here we describe a case with early‐onset epileptic encephalopathy, in whom exome sequencing detected a novel pathogenic homozygous c.442G>A, p.(Glu148Lys) variant in TBC1D24. She showed severe developmental delay, congenital sensorineural hearing loss and seizures, but the combination of a high dose phenobarbital and potassium bromide was very effective for the seizures. Sanger sequencing revealed that her mother was a heterozygous carrier of the TBC1D24 variant, but her father showed only wild‐type alleles. Homozygosity mapping analysis using exome data showed loss of the heterozygosity region at 16p13.3–p13.13 encompassing TBC1D24. Genotyping analysis using rare variants within loss of the heterozygosity region indicated that the patient has a homozygous haplotype inherited from her mother, indicating maternal segmental uniparental isodisomy (UPiD). These data clearly show that exome sequencing is a powerful tool to perform comprehensive genetic analysis.