Identification of a rare homozygous c.790C>T variation in the TFB2M gene in Korean patients with autism spectrum disorder
- Authors
- Park, Chan Bae; Choi, Vit-Na; Jun, Jae-Bum; Kim, Ji-Hae; Lee, Youngsoo; Lee, Jinhyuk; Lim, GyuTae; Kim, Jeonghyun; Jeong, Seon-Yong; Yim, Shin-Young
- Issue Date
- Dec-2018
- Publisher
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Keywords
- Autism spectrum disorder; Transcription factors; TFB2M; Mitochondria; Reactive oxygen species
- Citation
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.507, no.1-4, pp.148 - 154
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Volume
- 507
- Number
- 1-4
- Start Page
- 148
- End Page
- 154
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/2654
- DOI
- 10.1016/j.bbrc.2018.10.194
- ISSN
- 0006-291X
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 의과대학 > 서울 내과학교실 > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/2654)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.