title: A novel mutation of Hyaluronan synthase 2 gene in Chinese children with ventricular septal defect.
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.
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China ; National Research Institute for Family Planning, Beijing, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Deng
authors.affiliation: Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Guangying
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Research Institute for Family Planning, Beijing, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Yang
authors.affiliation: National Research Institute for Family Planning, Beijing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China ; National Research Institute for Family Planning, Beijing, China ; World Health Organization Collaborating Centre for Research in Human Reproduction, Beijing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Graduate School of Peking Union Medical College, Beijing, China ; National Research Institute for Family Planning, Beijing, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000886:Anthropometry; D016022:Case-Control Studies; D002648:Child; D002681:China; D019295:Computational Biology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004452:Echocardiography; D005091:Exons; D017353:Gene Deletion; D014453:Glucuronosyltransferase / Q000235:genetics*; D057809:HEK293 Cells; D006345:Heart Septal Defects, Ventricular / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D000076002:Hyaluronan Synthases; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D016366:Open Reading Frames; D017386:Sequence Homology, Amino Acid
chemical_list: D017931:DNA Primers; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases