155 572

Cited 0 times in

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

Authors
Park, CB  | Choi, VN | Jun, JB | Kim, JH | Lee, Y  | Lee, J | Lim, G | Kim, J  | Jeong, SY  | Yim, SY
Citation
Biochemical and biophysical research communications, 507(1-4). : 148-154, 2018
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
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 TFB2M mutations and variations involved in any human diseases. We identified a rare homozygous c.790C>T (His264Tyr) variation in TFB2M gene in 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.
Keywords
MeSH

DOI
10.1016/j.bbrc.2018.10.194
PMID
30414672
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Medical Genetics
Journal Papers > School of Medicine / Graduate School of Medicine > Physical Medicine & Rehabilitation
Ajou Authors
김, 정현  |  박, 찬배  |  이, 영수  |  임, 신영  |  정, 선용
Files in This Item:
30414672.pdfDownload
Export

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse