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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.

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Effect of E499V mutation on subcellular localization of HAS2.293T cells were transfected with empty vector pEGFP-N1, pEGFP-HAS2 wild-type, and the E499V mutant separately. After 30 h, transfected cells were then analyzed with an inverted fluorescence microscope to study the protein localization.
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pone-0087437-g003: Effect of E499V mutation on subcellular localization of HAS2.293T cells were transfected with empty vector pEGFP-N1, pEGFP-HAS2 wild-type, and the E499V mutant separately. After 30 h, transfected cells were then analyzed with an inverted fluorescence microscope to study the protein localization.

Mentions: The effect of the mutation on the cellular localization of HAS2 was observed using subcellular localization. As shown in Fig. 3, GFP (control) was located in both the nucleus and cytoplasm, while both of wild-type and mutant HAS2 fusion proteins were mainly detected in the plasma membrane and cytoplasm of 293T cells. So the HAS2 mutation didn't alter its nuclear localization pattern.


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 subcellular localization of HAS2.293T cells were transfected with empty vector pEGFP-N1, pEGFP-HAS2 wild-type, and the E499V mutant separately. After 30 h, transfected cells were then analyzed with an inverted fluorescence microscope to study the protein localization.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0087437-g003: Effect of E499V mutation on subcellular localization of HAS2.293T cells were transfected with empty vector pEGFP-N1, pEGFP-HAS2 wild-type, and the E499V mutant separately. After 30 h, transfected cells were then analyzed with an inverted fluorescence microscope to study the protein localization.
Mentions: The effect of the mutation on the cellular localization of HAS2 was observed using subcellular localization. As shown in Fig. 3, GFP (control) was located in both the nucleus and cytoplasm, while both of wild-type and mutant HAS2 fusion proteins were mainly detected in the plasma membrane and cytoplasm of 293T cells. So the HAS2 mutation didn't alter its nuclear localization pattern.

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