Scholarlink

<p>Tetralogy of Fallot (TOF) aetiologies remain largely unknown. Although syndromes with genetic cause have been involved, non-syndromic TOF are not completely elucidated, with a genetic diagnosis in less than 20% of the cases. <i>HEY2</i> is a basic helix-loop-helix (bHLH) repressive transcription factor implicated in cardiac development. In this study, we identify a novel heterozygous missense variant in <i>HEY2</i> gene segregating within a family presenting with non-syndromic TOF with autosomal dominant transmission. The identified variation c.171 G &gt; C p.(Glu57Asp) was tested through gene reporter assay, revealing a complete disruption of HEY2 repressive activity. These results suggest that HEY2 is a novel gene implicated in the pathogenesis of Tetralogy of Fallot, expanding the genetic spectrum of this congenital heart defect and reinforcing the role of monogenic contributions in non-syndromic TOF.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A novel heterozygous pathogenic variant in HEY2 led to a familial form of non-syndromic Tetralogy of Fallot

  • 期刊论文

  • 发表日期：

    2025年6月6日

查看全文
  • Camille Bergès,
  • Fanny Laffargue,
  • Claire Dauphin,
  • Alex-Vincent Postma,
  • Jean-Benoit Thambo,
  • Caroline Rooryck

摘要

Tetralogy of Fallot (TOF) aetiologies remain largely unknown. Although syndromes with genetic cause have been involved, non-syndromic TOF are not completely elucidated, with a genetic diagnosis in less than 20% of the cases. HEY2 is a basic helix-loop-helix (bHLH) repressive transcription factor implicated in cardiac development. In this study, we identify a novel heterozygous missense variant in HEY2 gene segregating within a family presenting with non-syndromic TOF with autosomal dominant transmission. The identified variation c.171 G > C p.(Glu57Asp) was tested through gene reporter assay, revealing a complete disruption of HEY2 repressive activity. These results suggest that HEY2 is a novel gene implicated in the pathogenesis of Tetralogy of Fallot, expanding the genetic spectrum of this congenital heart defect and reinforcing the role of monogenic contributions in non-syndromic TOF.