GATA4 Loss‐of‐Function Mutations Underlie Familial Tetralogy of Fallot. Issue 12 (17th September 2013)

• Record Type: Journal Article
• Authors: Yang, Yi‐Qing; Gharibeh, Lara; Li, Ruo‐Gu; Xin, Yuan‐Feng; Wang, Juan; Liu, Zhong‐Min; Qiu, Xing‐Biao; Xu, Ying‐Jia; Xu, Lei; Qu, Xin‐Kai; Liu, Xu; Fang, Wei‐Yi; Huang, Ri‐Tai; Xue, Song; Nemer, Georges
• Is Part Of: Human mutation. Volume 34:Issue 12(2013:Dec.)
• Page Start: 1662
• Page End: 1671
• Publication Date: 2013-09-17
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22434
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="graphical" xml:lang="en" id="humu22434-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>In this study, three novel heterozygous GATA4 mutations, A9P, L51V and N285S, were identified in three families with tetralogy of Fallot (TOF), respectively. In each family the mutation cosegregated with TOF with complete penetrance. Functional analysis showed that the GATA4 mutants were consistently associated with diminished DNA‐binding affinity and decreased transcriptional activity, although they completely translocated into the nuclei with normal nuclear distribution. Furthermore, the N285S mutation completely disrupted the physical interaction between GATA4 and TBX5 <boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg3wjb509c" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>