A novel mutation of Hyaluronan synthase 2 gene in Chinese children with ventricular septal defect

PLoS One. 2014 Feb 18;9(2):e87437. doi: 10.1371/journal.pone.0087437. eCollection 2014.

Abstract

As a major product of extracellular matrix (ECM), Hyaluronic acid (HA) is involved in early cardiac development and mainly synthesized by Hyaluronan synthase 2 (HAS2) during embryogenesis. Targeted deletion of HAS2 gene in mice led to obvious cardiac and vascular defects. To clarify the potential association of the mutation in HAS2 with the development of congenital heart disease (CHD), in this study, we sequenced the coding region of HAS2 and identified a novel non-synonymous variant c.A1496T (p.Glu499Val) in one of 100 non-syndromic Ventricular Septal Defect (VSD) patients. The variant was not observed in 250 controls. In addition, to determine the contribution of HAS2 variant in VSD, we compared HA content in supernatant using HA quantitative analysis and found that the mutation obviously affected the HA synthetic activity of HAS2. To our knowledge, this is the first time that the mutation in HAS2 was found in Chinese VSD patients, which suggested that HAS2 may be involved in the etiology of non-syndromic VSD and have the vital function in the development of heart septum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anthropometry
  • Case-Control Studies
  • Child
  • China
  • Computational Biology
  • DNA Mutational Analysis
  • DNA Primers / genetics
  • Echocardiography
  • Exons
  • Gene Deletion
  • Glucuronosyltransferase / genetics*
  • HEK293 Cells
  • Heart Septal Defects, Ventricular / ethnology
  • Heart Septal Defects, Ventricular / genetics*
  • Humans
  • Hyaluronan Synthases
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation*
  • Open Reading Frames
  • Sequence Homology, Amino Acid

Substances

  • DNA Primers
  • Glucuronosyltransferase
  • HAS2 protein, human
  • Hyaluronan Synthases

Grants and funding

This work was supported by the National Basic Research Program of China (2010CB5295040, http://www.973.gov.cn/English/Index.aspx) and the National Natural Science Foundation of China (81300131, http://www.nsfc.gov.cn/publish/portal0/default.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.