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De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature
BACKGROUND: Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association betwee...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574214/ https://www.ncbi.nlm.nih.gov/pubmed/26376624 http://dx.doi.org/10.1186/s12864-015-1898-1 |
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author | Yu, Yongguo Yao, RuEn Wang, Lili Fan, Yanjie Huang, Xiaodong Hirschhorn, Joel Dauber, Andrew Shen, Yiping |
author_facet | Yu, Yongguo Yao, RuEn Wang, Lili Fan, Yanjie Huang, Xiaodong Hirschhorn, Joel Dauber, Andrew Shen, Yiping |
author_sort | Yu, Yongguo |
collection | PubMed |
description | BACKGROUND: Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form. RESULTS: Based on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found. CONCLUSION: These results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non-syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1898-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4574214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-45742142015-09-19 De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature Yu, Yongguo Yao, RuEn Wang, Lili Fan, Yanjie Huang, Xiaodong Hirschhorn, Joel Dauber, Andrew Shen, Yiping BMC Genomics Research Article BACKGROUND: Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form. RESULTS: Based on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found. CONCLUSION: These results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non-syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1898-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-09-16 /pmc/articles/PMC4574214/ /pubmed/26376624 http://dx.doi.org/10.1186/s12864-015-1898-1 Text en © Yu et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Yu, Yongguo Yao, RuEn Wang, Lili Fan, Yanjie Huang, Xiaodong Hirschhorn, Joel Dauber, Andrew Shen, Yiping De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature |
title | De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature |
title_full | De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature |
title_fullStr | De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature |
title_full_unstemmed | De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature |
title_short | De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature |
title_sort | de novo mutations in arid1b associated with both syndromic and non-syndromic short stature |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574214/ https://www.ncbi.nlm.nih.gov/pubmed/26376624 http://dx.doi.org/10.1186/s12864-015-1898-1 |
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