Talk:Cardiovascular System - Double Outlet Right Ventricle

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On this website the Discussion Tab or "talk pages" for a topic has been used for several purposes: References - recent and historic that relates to the topic Additional topic information - currently prepared in draft format Links - to related webpages Topic page - an edit history as used on other Wiki sites Lecture/Practical - student feedback Student Projects - online project discussions. Links: Pubmed Most Recent | Reference Tutorial | Journal Searches Glossary Links Glossary: A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Symbols | Term Link Cite this page: Hill, M.A. (2026, September 30) Embryology Cardiovascular System - Double Outlet Right Ventricle. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Talk:Cardiovascular_System_-_Double_Outlet_Right_Ventricle

2017

HAND1 loss-of-function mutation contributes to congenital double outlet right ventricle

Int J Mol Med. 2017 Jan 20. doi: 10.3892/ijmm.2017.2865.

Li L1, Wang J2, Liu XY3, Liu H4, Shi HY4, Yang XX4, Li N4, Li YJ4, Huang RT5, Xue S5, Qiu XB4, Yang YQ4.

Abstract

Congenital heart defects (CHDs), a wide variety of developmental abnormalities in the structures of the heart and the great thoracic blood vessels, are the most common form of birth defect in humans worldwide. CHDs are accountable for substantial morbidity and are still the leading cause of birth defect‑related deaths. Recent studies have demonstrated the pivotal roles of genetic defects in the pathogenesis of CHDs, and a great number of genetic mutations have been associated with CHDs. Nevertheless, CHDs are a genetically heterogeneous disorder and the genetic basis underlying CHDs in an overwhelming majority of cases remains unclear. In the present study, the coding exons and flanking introns of the heart and neural crest derivatives expressed transcript 1 (HAND1) gene, which encodes a basic helix‑loop‑helix transcription factor crucial for cardiovascular development, were sequenced in 158 unrelated patients with CHDs, and a de novo heterozygous mutation, p.K132X, was identified in a patient with double outlet right ventricle (DORV), as well as ventricular septal defect. The nonsense mutation, which was predicted to produce a truncated HAND1 protein lacking 84 carboxyl‑terminal amino acids, was absent in 600 control chromosomes. Functional analyses revealed that the HAND1 K132X mutant had no transcriptional activity. Furthermore, the mutation disrupted the synergistic activation between HAND1 and GATA binding protein 4 (GATA4), another cardiac core transcription factor causally linked to CHDs. To the best of our knowledge, this is the first report on the association of HAND1 loss‑of‑function mutation with an enhanced susceptibility to DORV in humans. These findings expand the phenotypic spectrum linked to HAND1 mutations, suggesting potential implications for the development of novelo prophylactic and therapeutic strategies for DORV.

PMID 28112363 DOI: 10.3892/ijmm.2017.2865