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Title 

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

Authors 

C B ParkV N ChoiJ B JunJ H KimY LeeJinhyuk LeeGyuTae LimJ KimS Y JeongS Y Yim

Publisher 

Elsevier

Issue Date 

2018

Citation 

Biochemical and Biophysical Research Communications

Keywords 

Autism spectrum disorderMitochondriaReactive oxygen speciesTFB2MTranscription factors

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.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2018.10.194

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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