title: A novel mutation of GATA4 (K300T) associated with familial atrial septal defect.
abstract: The GATA-binding protein 4 gene (GATA4) encodes a zinc-finger transcription factor that plays a key role in embryogenesis and cardiac development. Variants in the GATA4 gene have been implicated in several congenital heart diseases (CHD), such as the tetralogy of Fallot (ToF), atrial septal defect (ASD), ventricular septal defect (VSD), atrioventricular septal defect (AVSD), and dilated cardiomyopathy (DCM). We studied a four-generation Chinese ASD family and identified a novel GATA4 mutation (c.A899C, p.K300T) in all surviving affected members and two carriers with incomplete penetrance. Bioinformatics programs (PolyPhen-2, SIFT, and MutationTaster) predicted the mutation to be deleterious. The lysine at the mutation position was highly conserved from Drosophila to humans and was recognized as a methylation location in the GATA4 protein. The involvement of the lysine methylation in cardiogenesis by attenuating the transcriptional activity of GATA4 in mice has been previously examined. Our study broadens the mutation spectrum of the GATA4 gene and reveals for the first time a mutation at the methylation position of GATA4 associated with ASD.
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan province 410008, China. Electronic address: chenjia@sklmg.edu.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: China Japan Union Hospital, Jilin University, Changchun, Jilin province 130031, China. Electronic address: qiby14@mails.jlu.edu.cn.
authors.forename: Bingyang
authors.initials: B
authors.lastname: Qi
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan province 410008, China. Electronic address: zhaojuan@sklmg.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan province 410008, China. Electronic address: liuwei_nv@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Medical Genetics & School of Life Sciences, Central South University, Changsha, Hunan province 410008, China. Electronic address: duanranhui@sklmg.edu.cn.
authors.forename: Ranhui
authors.initials: R
authors.lastname: Duan
authors.affiliation: China Japan Union Hospital, Jilin University, Changchun, Jilin province 130031, China. Electronic address: zhangmingqiu62@126.com.
authors.forename: Mingqiu
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002681:China; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D008239:Lysine
keywords: Incomplete penetrance; Methylation; Post-translational modification; Ventricular septal defect; Whole exome sequencing