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Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree
BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect. Its etiology is complex and it has a lifelong influence on affected individuals. Despite many studies, the pathogenic gene alleles are not completely clear. Here, we recruited a Chi...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732289/ https://www.ncbi.nlm.nih.gov/pubmed/31386309 http://dx.doi.org/10.1002/mgg3.714 |
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author | Meng, Peiqi Zhao, Huaxiang Huang, Wenbin Zhang, Yunfan Zhong, Wenjie Zhang, Mengqi Jia, Peizeng Zhou, Zhibo Maimaitili, Gulibaha Chen, Feng Zhang, Jieni Lin, Jiuxiang |
author_facet | Meng, Peiqi Zhao, Huaxiang Huang, Wenbin Zhang, Yunfan Zhong, Wenjie Zhang, Mengqi Jia, Peizeng Zhou, Zhibo Maimaitili, Gulibaha Chen, Feng Zhang, Jieni Lin, Jiuxiang |
author_sort | Meng, Peiqi |
collection | PubMed |
description | BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect. Its etiology is complex and it has a lifelong influence on affected individuals. Despite many studies, the pathogenic gene alleles are not completely clear. Here, we recruited a Chinese NSCL/P family and explored the candidate causative variants in this pedigree. METHODS: We performed whole‐exome sequencing on two patients and two unaffected subjects of this family. Variants were screened based on bioinformatics analysis to identify the potential etiological alleles. Species conservation analysis, mutation function prediction, and homology protein modeling were also performed to preliminarily evaluate the influence of the mutations. RESULTS: We identified three rare mutations that are located on a single chromatid (c.2684C > T_p.Ala895Val, c.4350G > T_p.Gln1450His, and c.4622C > A_p.Ser1541Tyr) in GLI2 as candidate causative variants. All of these three mutations were predicted to be deleterious, and they affect amino acids that are conserved in many species. The mutation c.2684C > T was predicted to affect the structure of the GLI2 protein. CONCLUSION: Our results further demonstrate that GLI2 variants play a role in the pathogenesis of NSCL/P, and the three rare missense mutations combined are probably the potential disease‐causing variants in this family. |
format | Online Article Text |
id | pubmed-6732289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67322892019-09-12 Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree Meng, Peiqi Zhao, Huaxiang Huang, Wenbin Zhang, Yunfan Zhong, Wenjie Zhang, Mengqi Jia, Peizeng Zhou, Zhibo Maimaitili, Gulibaha Chen, Feng Zhang, Jieni Lin, Jiuxiang Mol Genet Genomic Med Original Articles BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect. Its etiology is complex and it has a lifelong influence on affected individuals. Despite many studies, the pathogenic gene alleles are not completely clear. Here, we recruited a Chinese NSCL/P family and explored the candidate causative variants in this pedigree. METHODS: We performed whole‐exome sequencing on two patients and two unaffected subjects of this family. Variants were screened based on bioinformatics analysis to identify the potential etiological alleles. Species conservation analysis, mutation function prediction, and homology protein modeling were also performed to preliminarily evaluate the influence of the mutations. RESULTS: We identified three rare mutations that are located on a single chromatid (c.2684C > T_p.Ala895Val, c.4350G > T_p.Gln1450His, and c.4622C > A_p.Ser1541Tyr) in GLI2 as candidate causative variants. All of these three mutations were predicted to be deleterious, and they affect amino acids that are conserved in many species. The mutation c.2684C > T was predicted to affect the structure of the GLI2 protein. CONCLUSION: Our results further demonstrate that GLI2 variants play a role in the pathogenesis of NSCL/P, and the three rare missense mutations combined are probably the potential disease‐causing variants in this family. John Wiley and Sons Inc. 2019-08-06 /pmc/articles/PMC6732289/ /pubmed/31386309 http://dx.doi.org/10.1002/mgg3.714 Text en © 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Meng, Peiqi Zhao, Huaxiang Huang, Wenbin Zhang, Yunfan Zhong, Wenjie Zhang, Mengqi Jia, Peizeng Zhou, Zhibo Maimaitili, Gulibaha Chen, Feng Zhang, Jieni Lin, Jiuxiang Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree |
title | Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree |
title_full | Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree |
title_fullStr | Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree |
title_full_unstemmed | Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree |
title_short | Three GLI2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a Chinese pedigree |
title_sort | three gli2 mutations combined potentially underlie non‐syndromic cleft lip with or without cleft palate in a chinese pedigree |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732289/ https://www.ncbi.nlm.nih.gov/pubmed/31386309 http://dx.doi.org/10.1002/mgg3.714 |
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