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Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts

PURPOSE: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital coralliform cataracts and demonstrate the functional analysis of a candidate gene in the family. METHODS: Family history data were recorded. Clinical and ophthalmologic examinatio...

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Autores principales: Li, Feifeng, Wang, Shuzhen, Gao, Chang, Liu, Shiguo, Zhao, Baojian, Zhang, Meng, Huang, Shangzhi, Zhu, Siquan, Ma, Xu
Formato: Texto
Lenguaje:English
Publicado: Molecular Vision 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268897/
https://www.ncbi.nlm.nih.gov/pubmed/18334953
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author Li, Feifeng
Wang, Shuzhen
Gao, Chang
Liu, Shiguo
Zhao, Baojian
Zhang, Meng
Huang, Shangzhi
Zhu, Siquan
Ma, Xu
author_facet Li, Feifeng
Wang, Shuzhen
Gao, Chang
Liu, Shiguo
Zhao, Baojian
Zhang, Meng
Huang, Shangzhi
Zhu, Siquan
Ma, Xu
author_sort Li, Feifeng
collection PubMed
description PURPOSE: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital coralliform cataracts and demonstrate the functional analysis of a candidate gene in the family. METHODS: Family history data were recorded. Clinical and ophthalmologic examinations were performed on affected and unaffected family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated using the Linkage software after genotyping. A mutation was detected by direct sequencing, using gene-specific primers. Wild-type and mutant proteins were analyzed with online software. RESULTS: Affected members of this family had coralliform cataracts. Linkage analysis was obtained at markers, D2S72 (LOD score [Z]=3.31, recombination fraction [θ]=0.0) and D2S1782 (Z=3.01, θ=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the γD-crystallin gene (CRYGD) revealed a G>T transversion in exon 2, which caused a conservative substitution of Gly to Cys at codon 61 (P.G61C). This mutation co-segregated with the disease phenotype in all affected individuals and was not observed in any of the unaffected or 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Gly61. Data generated with online software revealed that the mutation altered the protein’s stability, solvent-accessibility, and interactions with other proteins. CONCLUSIONS: This is the first reported case of a congenital coralliform cataract phenotype associated with the mutation of Gly61Cys (P.G61C) in the CRYGD gene; it demonstrates a possible mechanism of action for the mutant gene.
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spelling pubmed-22688972008-03-20 Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts Li, Feifeng Wang, Shuzhen Gao, Chang Liu, Shiguo Zhao, Baojian Zhang, Meng Huang, Shangzhi Zhu, Siquan Ma, Xu Mol Vis Research Article PURPOSE: We sought to identify the genetic defect in a four-generation Chinese family with autosomal dominant congenital coralliform cataracts and demonstrate the functional analysis of a candidate gene in the family. METHODS: Family history data were recorded. Clinical and ophthalmologic examinations were performed on affected and unaffected family members. All the members were genotyped with microsatellite markers at loci considered to be associated with cataracts. Two-point LOD scores were calculated using the Linkage software after genotyping. A mutation was detected by direct sequencing, using gene-specific primers. Wild-type and mutant proteins were analyzed with online software. RESULTS: Affected members of this family had coralliform cataracts. Linkage analysis was obtained at markers, D2S72 (LOD score [Z]=3.31, recombination fraction [θ]=0.0) and D2S1782 (Z=3.01, θ=0.0). Haplotype analysis indicated that the cataract gene was closely linked to these two markers. Sequencing the γD-crystallin gene (CRYGD) revealed a G>T transversion in exon 2, which caused a conservative substitution of Gly to Cys at codon 61 (P.G61C). This mutation co-segregated with the disease phenotype in all affected individuals and was not observed in any of the unaffected or 100 normal, unrelated individuals. Bioinformatic analyses showed that a highly conserved region was located around Gly61. Data generated with online software revealed that the mutation altered the protein’s stability, solvent-accessibility, and interactions with other proteins. CONCLUSIONS: This is the first reported case of a congenital coralliform cataract phenotype associated with the mutation of Gly61Cys (P.G61C) in the CRYGD gene; it demonstrates a possible mechanism of action for the mutant gene. Molecular Vision 2008-03-04 /pmc/articles/PMC2268897/ /pubmed/18334953 Text en http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Feifeng
Wang, Shuzhen
Gao, Chang
Liu, Shiguo
Zhao, Baojian
Zhang, Meng
Huang, Shangzhi
Zhu, Siquan
Ma, Xu
Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts
title Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts
title_full Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts
title_fullStr Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts
title_full_unstemmed Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts
title_short Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform cataracts
title_sort mutation g61c in the crygd gene causing autosomal dominant congenital coralliform cataracts
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268897/
https://www.ncbi.nlm.nih.gov/pubmed/18334953
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