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DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome

Congenital heart diseases (CHDs) are the most common types of birth defects, affecting approximately 1% of live births and remaining the leading cause of mortality. CHD patients often show a higher incidence of heterotaxy syndrome. However, the exact aetiology of CHD and heterotaxy syndrome remains...

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Autores principales: Liu, Sida, Chen, Weicheng, Zhan, Yongkun, Li, Shuolin, Ma, Xiaojing, Ma, Duan, Sheng, Wei, Huang, Guoying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491566/
https://www.ncbi.nlm.nih.gov/pubmed/31040315
http://dx.doi.org/10.1038/s41598-019-43109-6
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author Liu, Sida
Chen, Weicheng
Zhan, Yongkun
Li, Shuolin
Ma, Xiaojing
Ma, Duan
Sheng, Wei
Huang, Guoying
author_facet Liu, Sida
Chen, Weicheng
Zhan, Yongkun
Li, Shuolin
Ma, Xiaojing
Ma, Duan
Sheng, Wei
Huang, Guoying
author_sort Liu, Sida
collection PubMed
description Congenital heart diseases (CHDs) are the most common types of birth defects, affecting approximately 1% of live births and remaining the leading cause of mortality. CHD patients often show a higher incidence of heterotaxy syndrome. However, the exact aetiology of CHD and heterotaxy syndrome remains unclear. In this study, targeted sequencing and Sanger sequencing were performed to analyze the exonic regions of 37 primary ciliary dysfunction (PCD)- related candidate genes in 42 CHD patients with heterotaxy syndrome. Variants affecting protein-coding regions were filtered according to databases of known variants and predicted in silico using functional prediction program. Thirty-four potential disease-causing heterozygous variants in 11 genes were identified in the 19 CHD patients with heterotaxy syndrome (45.2%, 19/42). The DNAH11 gene showed the highest mutation rate (16.7%; 14 of 84 alleles) among the CHD patients with heterotaxy. Fisher’s exact test revealed a significant association of DNAH11 variants with CHD and heterotaxy (P = 0.0001). In families, six different compound heterozygous variants of DNAH11 were validated in family 1-5031 (p.W802X/p.M282I), family 2-5045 (p.T3460K/p.G4425S), family 3-5065 (p.G447R/p.L1157R), family 4-5130 (p.I2262T/p.D3800H), family 5-5707 (p.S1823fs/p.F2759L/p.R4395X) and family 6-5062 (p.D3610V/p.I243V). These findings suggest that the DNAH11 variants are significantly associated with CHD and heterotaxy syndrome and that compound heterozygous DNAH11 variants may be the common genetic cause of the development of familial CHD and heterotaxy syndrome.
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spelling pubmed-64915662019-05-17 DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome Liu, Sida Chen, Weicheng Zhan, Yongkun Li, Shuolin Ma, Xiaojing Ma, Duan Sheng, Wei Huang, Guoying Sci Rep Article Congenital heart diseases (CHDs) are the most common types of birth defects, affecting approximately 1% of live births and remaining the leading cause of mortality. CHD patients often show a higher incidence of heterotaxy syndrome. However, the exact aetiology of CHD and heterotaxy syndrome remains unclear. In this study, targeted sequencing and Sanger sequencing were performed to analyze the exonic regions of 37 primary ciliary dysfunction (PCD)- related candidate genes in 42 CHD patients with heterotaxy syndrome. Variants affecting protein-coding regions were filtered according to databases of known variants and predicted in silico using functional prediction program. Thirty-four potential disease-causing heterozygous variants in 11 genes were identified in the 19 CHD patients with heterotaxy syndrome (45.2%, 19/42). The DNAH11 gene showed the highest mutation rate (16.7%; 14 of 84 alleles) among the CHD patients with heterotaxy. Fisher’s exact test revealed a significant association of DNAH11 variants with CHD and heterotaxy (P = 0.0001). In families, six different compound heterozygous variants of DNAH11 were validated in family 1-5031 (p.W802X/p.M282I), family 2-5045 (p.T3460K/p.G4425S), family 3-5065 (p.G447R/p.L1157R), family 4-5130 (p.I2262T/p.D3800H), family 5-5707 (p.S1823fs/p.F2759L/p.R4395X) and family 6-5062 (p.D3610V/p.I243V). These findings suggest that the DNAH11 variants are significantly associated with CHD and heterotaxy syndrome and that compound heterozygous DNAH11 variants may be the common genetic cause of the development of familial CHD and heterotaxy syndrome. Nature Publishing Group UK 2019-04-30 /pmc/articles/PMC6491566/ /pubmed/31040315 http://dx.doi.org/10.1038/s41598-019-43109-6 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Liu, Sida
Chen, Weicheng
Zhan, Yongkun
Li, Shuolin
Ma, Xiaojing
Ma, Duan
Sheng, Wei
Huang, Guoying
DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome
title DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome
title_full DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome
title_fullStr DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome
title_full_unstemmed DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome
title_short DNAH11 variants and its association with congenital heart disease and heterotaxy syndrome
title_sort dnah11 variants and its association with congenital heart disease and heterotaxy syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6491566/
https://www.ncbi.nlm.nih.gov/pubmed/31040315
http://dx.doi.org/10.1038/s41598-019-43109-6
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