Haploinsufficiency of the basic helix-loop-helix transcription factor HAND2 causes congenital heart defects

American Journal of Medical Genetics. Part a
Ana S A CohenRam Singh

Abstract

Congenital heart defects (CHDs) are caused by a disruption in heart morphogenesis, which is dependent, in part, on a network of transcription factors (TFs) that regulate myocardial development. Heterozygous sequence variants in the basic helix-loop-helix TF gene heart and neural crest derivatives expressed 2 (HAND2) have been reported among some patients with CHDs; however, HAND2 has not yet been established as a Mendelian disease gene. We report a 31-month-old male with unicommissural unicuspid aortic valve, moderate aortic stenosis, and mild pulmonic stenosis. Chromosome analysis revealed a normal 46,XY karyotype, and a CHD sequencing panel was negative for pathogenic variants in NKX2.5, GATA4, TBX5, and CHD7. However, chromosomal microarray (CMA) testing identified a heterozygous 546.0-kb deletion on chromosome 4q34.1 (174364195_174910239[GRCh37/hg19]) that included exons 1 and 2 of SCRG1, HAND2, and HAND2-AS1. Familial CMA testing determined that the deletion was paternally inherited, which supported a likely pathogenic classification as the proband's father had previously undergone surgery for Tetralogy of Fallot. The family history was also notable for a paternal uncle who had previously died from complications related to...Continue Reading

References

Jul 11, 1998·The Journal of Biological Chemistry·M DronM G Tovey
Dec 9, 2003·Trends in Molecular Medicine·Cathy J HatcherCraig T Basson
May 20, 2005·The Journal of Clinical Investigation·Elisabeth M ZeisbergWilliam T Pu
Nov 15, 2008·Circulation Research·Yuka Morikawa, Peter Cserjesi
Oct 27, 2010·PLoS Genetics·Ni HuangMatthew E Hurles
Aug 1, 2012·American Journal of Medical Genetics. Part a·Eugen-Matthias StrehleTaosheng Huang
Sep 4, 2012·American Journal of Human Genetics·Rachel SoemediBernard D Keavney
Nov 1, 2013·Nucleic Acids Research·Jeffrey R MacDonaldStephen W Scherer
Dec 18, 2015·International Journal of Molecular Medicine·Cai-Xia LuYi-Qing Yang
Feb 13, 2016·G3 : Genes - Genomes - Genetics·Yu-Min SunYi-Qing Yang
Sep 16, 2018·European Journal of Medical Genetics·Hua LiuYi-Qing Yang
Oct 6, 2018·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Rajani M George, Anthony B Firulli

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Citations

Jun 13, 2021·Cold Spring Harbor Molecular Case Studies·Ram SinghEthylin Wang Jabs

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