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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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The alignment of the HAS2 sequence with the corresponding segments in different species was shown.It indicates that glutamic acid at position 499 is highly conserved. The black arrow indicates high conservation.
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pone-0087437-g002: The alignment of the HAS2 sequence with the corresponding segments in different species was shown.It indicates that glutamic acid at position 499 is highly conserved. The black arrow indicates high conservation.

Mentions: In the patient group, a novel non-synonymous substitution of c.A1496T (p.Glu499Val) was detected in a 6-year-old child (Fig. 1). Glu499 was highly conserved among many species (human, mice, rat, chimpanzee, dog, cow, chicken and zebrafish, shown in Fig. 2). The variant was not found in 250 controls and has not been listed in the NHLBI Exome Sequencing Project (ESP) Exome Variant Server, EvoSNP-DB, the NCBI dbSNP and the 1000 Genome Project database (http://browser.1000genomes.org/). Using two different algorithms (PolyPhen and Sift Functional analysis) to predict the effect of the mutation on HAS2 function, the novel non-synonymous substitution (p.Glu499Val) may be damaging.


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)

The alignment of the HAS2 sequence with the corresponding segments in different species was shown.It indicates that glutamic acid at position 499 is highly conserved. The black arrow indicates high conservation.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0087437-g002: The alignment of the HAS2 sequence with the corresponding segments in different species was shown.It indicates that glutamic acid at position 499 is highly conserved. The black arrow indicates high conservation.
Mentions: In the patient group, a novel non-synonymous substitution of c.A1496T (p.Glu499Val) was detected in a 6-year-old child (Fig. 1). Glu499 was highly conserved among many species (human, mice, rat, chimpanzee, dog, cow, chicken and zebrafish, shown in Fig. 2). The variant was not found in 250 controls and has not been listed in the NHLBI Exome Sequencing Project (ESP) Exome Variant Server, EvoSNP-DB, the NCBI dbSNP and the 1000 Genome Project database (http://browser.1000genomes.org/). Using two different algorithms (PolyPhen and Sift Functional analysis) to predict the effect of the mutation on HAS2 function, the novel non-synonymous substitution (p.Glu499Val) may be damaging.

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