A case of early‐onset epileptic encephalopathy with a homozygous TBC1D24 variant caused by uniparental isodisomy. Issue 4 (24th January 2019)

• Record Type: Journal Article
• Authors: Nakashima, Mitsuko; Negishi, Yutaka; Hori, Ikumi; Hattori, Ayako; Saitoh, Shinji; Saitsu, Hirotomo
• Is Part Of: American journal of medical genetics. Volume 179:Issue 4(2019)
• Page Start: 645
• Page End: 649
• Publication Date: 2019-01-24
• Subjects: epileptic encephalopathy -- exome sequencing -- loss of the heterozygosity -- TBC1D24 -- uniparental isodisomy; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61056
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : 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.