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Identification of a rare homozygous c.790C>T variation in the TFB2M gene in Korean patients with aut
2019-08-09 14:17:06
 2018 Dec 9;507(1-4):148-154. doi: 10.1016/j.bbrc.2018.10.194. Epub 2018 Nov 7.

Identification of a rare homozygous c.790C>T variation in the TFB2M gene in Korean patientswith autism spectrum disorder.


Mitochondrial dysfunction and subsequent enhanced oxidative stress is implicated in the pathogenesis of autism spectrum disorder (ASD). Mitochondrial transcription factor B2 (TFB2M) is an essential protein in mitochondrial gene expression. No reports have described TFB2Mmutations and variations involved in any human diseases. We identified a rare homozygous c.790C>T (His264Tyr) variation in TFB2M genein two Korean siblings with ASD by whole-exome sequencing. The roles of the TFB2M variation in the pathogenesis of ASD were investigated. Patient fibroblasts revealed increased transcription of mitochondrial genes and mitochondrial function in terms of ATP, membrane potential, oxygen consumption, and reactive oxygen species (ROS). Overexpression of the TFB2M variant in primary-cultured fibroblasts demonstrated significantly increased transcription of mitochondrial genes and mitochondrial function compared with overexpression of wild-type TFB2M. Molecular dynamics simulation of the TFB2M variant protein suggested an increase in the rigidity of the hinge region, which may cause alterations in loading and/or unloading of TFB2M on target DNA. Our results suggest that augmentation of mitochondrial gene expression and subsequent enhancement of mitochondrial function may be associated with the pathogenesis of ASD in Korean patients.


Autism spectrum disorder; Mitochondria; Reactive oxygen species; TFB2M; Transcription factors

PMID: 30414672  DOI:10.1016/j.bbrc.2018.10.194

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