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PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population
The present study aimed to identify the disease-causing gene of a four-generation Chinese family affected with congenital posterior subcapsular cataracts (CPSC), to additionally investigate the frequency of paired like homeodomain 3 (PITX3) mutations in Chinese patients with autosomal dominant conge...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423573/ https://www.ncbi.nlm.nih.gov/pubmed/30816539 http://dx.doi.org/10.3892/mmr.2019.9989 |
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author | Wu, Zehua Meng, Delong Fang, Chengbo Li, Jian Zheng, Xiujie Lin, Jiansuo Zeng, Haijiang Lv, Sihan Zhang, Zhenning Luan, Bing Zhong, Zilin Chen, Jianjun |
author_facet | Wu, Zehua Meng, Delong Fang, Chengbo Li, Jian Zheng, Xiujie Lin, Jiansuo Zeng, Haijiang Lv, Sihan Zhang, Zhenning Luan, Bing Zhong, Zilin Chen, Jianjun |
author_sort | Wu, Zehua |
collection | PubMed |
description | The present study aimed to identify the disease-causing gene of a four-generation Chinese family affected with congenital posterior subcapsular cataracts (CPSC), to additionally investigate the frequency of paired like homeodomain 3 (PITX3) mutations in Chinese patients with autosomal dominant congenital cataract (ADCC) and to analyze the pathogenesis of the mutations identified in the present study. Whole exome sequencing (WES) was utilized to identify the genetic cause of CPSC in the four-generation family. Sanger sequencing was performed to verify the WES results and to screen for mutations of the PITX3 gene in probands of an additional 194 Chinese ADCC families. Co-segregation analysis was performed in the family members with available DNA. Subcellular localization analyses and transactivation assays were performed for the PITX3 mutations identified. From the WES data, the c.608delC (p.A203GfsX106) mutation of PITX3 was identified in the four-generation family with CPSC. A second PITX3 mutation c.640_656del (p.A214RfsX42) was detected in two of the additional 194 ADCC families and one of these two families exhibited incomplete penetrance. Functional studies indicated that these 2 PITX3 mutant proteins retained a nuclear localization pattern, but resulted in decreased transactivation activity, similar to other previously identified PITX3 mutations. In the present study, 2 different mutations (p.A203GfsX106 and p.A214RfsX42) in PITX3 were identified as the causative defect in a four-generation family with CPSC and two ADCC families, respectively. The prevalence of PITX3 gene-associated cataract was 1.54% (3/195) in the Chinese congenital cataract (CC) family cohort. In vitro functional analyses of these 2 PITX3 mutations were performed, in order to enhance understanding of the pathogenesis of CC caused by PITX3 mutations. |
format | Online Article Text |
id | pubmed-6423573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-64235732019-03-22 PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population Wu, Zehua Meng, Delong Fang, Chengbo Li, Jian Zheng, Xiujie Lin, Jiansuo Zeng, Haijiang Lv, Sihan Zhang, Zhenning Luan, Bing Zhong, Zilin Chen, Jianjun Mol Med Rep Articles The present study aimed to identify the disease-causing gene of a four-generation Chinese family affected with congenital posterior subcapsular cataracts (CPSC), to additionally investigate the frequency of paired like homeodomain 3 (PITX3) mutations in Chinese patients with autosomal dominant congenital cataract (ADCC) and to analyze the pathogenesis of the mutations identified in the present study. Whole exome sequencing (WES) was utilized to identify the genetic cause of CPSC in the four-generation family. Sanger sequencing was performed to verify the WES results and to screen for mutations of the PITX3 gene in probands of an additional 194 Chinese ADCC families. Co-segregation analysis was performed in the family members with available DNA. Subcellular localization analyses and transactivation assays were performed for the PITX3 mutations identified. From the WES data, the c.608delC (p.A203GfsX106) mutation of PITX3 was identified in the four-generation family with CPSC. A second PITX3 mutation c.640_656del (p.A214RfsX42) was detected in two of the additional 194 ADCC families and one of these two families exhibited incomplete penetrance. Functional studies indicated that these 2 PITX3 mutant proteins retained a nuclear localization pattern, but resulted in decreased transactivation activity, similar to other previously identified PITX3 mutations. In the present study, 2 different mutations (p.A203GfsX106 and p.A214RfsX42) in PITX3 were identified as the causative defect in a four-generation family with CPSC and two ADCC families, respectively. The prevalence of PITX3 gene-associated cataract was 1.54% (3/195) in the Chinese congenital cataract (CC) family cohort. In vitro functional analyses of these 2 PITX3 mutations were performed, in order to enhance understanding of the pathogenesis of CC caused by PITX3 mutations. D.A. Spandidos 2019-04 2019-02-26 /pmc/articles/PMC6423573/ /pubmed/30816539 http://dx.doi.org/10.3892/mmr.2019.9989 Text en Copyright: © Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Wu, Zehua Meng, Delong Fang, Chengbo Li, Jian Zheng, Xiujie Lin, Jiansuo Zeng, Haijiang Lv, Sihan Zhang, Zhenning Luan, Bing Zhong, Zilin Chen, Jianjun PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population |
title | PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population |
title_full | PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population |
title_fullStr | PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population |
title_full_unstemmed | PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population |
title_short | PITX3 mutations associated with autosomal dominant congenital cataract in the Chinese population |
title_sort | pitx3 mutations associated with autosomal dominant congenital cataract in the chinese population |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423573/ https://www.ncbi.nlm.nih.gov/pubmed/30816539 http://dx.doi.org/10.3892/mmr.2019.9989 |
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