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

Zhu X, Deng X, Huang G, Wang J, Yang J, Chen S, Ma X, Wang B - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Peking Union Medical College, Beijing, China ; National Research Institute for Family Planning, Beijing, China.

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.

Show MeSH

Related in: MedlinePlus

Effect of E499V mutation on HA synthesis. 293T cells were transfected with empty vector pcDNA3.1 (+), pcDNA3.1-HAS2 wild-type and the E499V mutant separately.HA content in media was determined as described in the methods section. Results are representative of three separate experiments. The significance of differences was calculated using the independent-samples t test. *p<0.05, **p<0.01 versus empty vector pcDNA3.1 (+); #p<0.05, ##p<0.01 versus wild-type.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3928120&req=5

pone-0087437-g004: Effect of E499V mutation on HA synthesis. 293T cells were transfected with empty vector pcDNA3.1 (+), pcDNA3.1-HAS2 wild-type and the E499V mutant separately.HA content in media was determined as described in the methods section. Results are representative of three separate experiments. The significance of differences was calculated using the independent-samples t test. *p<0.05, **p<0.01 versus empty vector pcDNA3.1 (+); #p<0.05, ##p<0.01 versus wild-type.

Mentions: HA quantitative assay was used to evaluate whether the mutation affected catalytic property of HAS2. We transfected the plasmid including wild-type or mutant HAS2 into 293T, and compared the production of HA. The wild-type HAS2 resulted in a 2.37-fold increase (t test, p<0.001) of HA production compared with control (pcDNA3.1 only). The mutant HAS2 resulted in an approximately 40% (t test, p<0.01) reduction of the catalytic activity compared with wild-type HAS2 (Fig. 4).


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

Zhu X, Deng X, Huang G, Wang J, Yang J, Chen S, Ma X, Wang B - PLoS ONE (2014)

Effect of E499V mutation on HA synthesis. 293T cells were transfected with empty vector pcDNA3.1 (+), pcDNA3.1-HAS2 wild-type and the E499V mutant separately.HA content in media was determined as described in the methods section. Results are representative of three separate experiments. The significance of differences was calculated using the independent-samples t test. *p<0.05, **p<0.01 versus empty vector pcDNA3.1 (+); #p<0.05, ##p<0.01 versus wild-type.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928120&req=5

pone-0087437-g004: Effect of E499V mutation on HA synthesis. 293T cells were transfected with empty vector pcDNA3.1 (+), pcDNA3.1-HAS2 wild-type and the E499V mutant separately.HA content in media was determined as described in the methods section. Results are representative of three separate experiments. The significance of differences was calculated using the independent-samples t test. *p<0.05, **p<0.01 versus empty vector pcDNA3.1 (+); #p<0.05, ##p<0.01 versus wild-type.
Mentions: HA quantitative assay was used to evaluate whether the mutation affected catalytic property of HAS2. We transfected the plasmid including wild-type or mutant HAS2 into 293T, and compared the production of HA. The wild-type HAS2 resulted in a 2.37-fold increase (t test, p<0.001) of HA production compared with control (pcDNA3.1 only). The mutant HAS2 resulted in an approximately 40% (t test, p<0.01) reduction of the catalytic activity compared with wild-type HAS2 (Fig. 4).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate School of Peking Union Medical College, Beijing, China ; National Research Institute for Family Planning, Beijing, China.

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.

Show MeSH
Related in: MedlinePlus