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TBX1 loss-of-function mutation contributes to congenital conotruncal defects 期刊论文

编号：

b1c1b5c4-a76f-4f44-b4a4-4d2b27c9aa97
作者：

Zhang, Min^[1] Li, FuXing^[2] Liu, XingYuan^[2] Hou, JingYi^[2] Ni, ShiHong^[3] Wang, Juan^[4] Zhao, CuiMei^[4] Zhang, Wei^[5] Kong, Ye^[5] Huang, RiTai^[6] Xue, Song^[6] Yang, YiQing^[7]
语种：

English
期刊：

EXPERIMENTAL AND THERAPEUTIC MEDICINE ISSN：1792-0981 2018 年 15 卷 1 期 (447 - 453) ; JAN
收录：
关键词：

congenital heart defect genetics transcription factors TBX1 reporter gene assay
摘要：

Conotruncal defects (CTDs) account for similar to 30% of all types of congenital heart disease and contribute to increased morbidity and mortality rates. Increasing evidence suggests that genetic risk factors are involved in the pathogenesis of CTDs. Mutations in a number of genes, including the TBX1 gene that codes for a T-box transcription factor essential for normal cardiovascular development, may contribute to the development of CTD. CTDs are genetically heterogeneous and the genetic defects responsible for CTDs in the majority of patients remain unknown. The present study sequenced the coding regions and splicing junction boundaries of TBX1 in 136 patients with CTDs and 300 matched healthy individuals. The disease-causing potential of the identified TBX1 sequence variation was evaluated using MutationTaster, PolyPhen-2, SIFT and PROVEN software. The functional characteristics of the mutant TBX1 gene were defined using a dual-luciferase reporter assay system. A novel heterozygous TBX1 mutation, p.S233Y, was identified in a patient with transposition of the great arteries (TGA) and a ventricular septal defect. This mutation was absent in the 300 controls and altered the amino acid produced, serine, which is evolutionarily conserved across several species, and was predicted to be pathogenic in silico. Luciferase assays conducted in COS-7 cells demonstrated that the newly identified TBX1 mutation was associated with significantly diminished transcriptional activation of the ANF promoter compared with the wild-type TBX1. To the best of our knowledge, the present study is the first to associate a TBX1 loss-of-function mutation with enhanced susceptibility to TGA, which adds significant insight to the molecular mechanism of TGA.
推荐引用方式
GB/T 7714：

Zhang Min,Li Fu-Xing,Liu Xing-Yuan, et al. TBX1 loss-of-function mutation contributes to congenital conotruncal defects [J].EXPERIMENTAL AND THERAPEUTIC MEDICINE,2018,15(1):447-453.
APA：

Zhang Min,Li Fu-Xing,Liu Xing-Yuan,Hou Jing-Yi,&Yang Yi-Qing.(2018).TBX1 loss-of-function mutation contributes to congenital conotruncal defects .EXPERIMENTAL AND THERAPEUTIC MEDICINE,15(1):447-453.
MLA：

Zhang Min, et al. "TBX1 loss-of-function mutation contributes to congenital conotruncal defects" .EXPERIMENTAL AND THERAPEUTIC MEDICINE 15,1(2018):447-453.

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