Dataset Information

A novel P20R mutation in the alpha-B crystallin gene causes autosomal dominant congenital posterior polar cataracts in a Chinese family.

ABSTRACT: BACKGROUND: To identify the genetic defects and investigate the possible mechanism of cataract genesis in a five-generation family with autosomal dominant congenital posterior polar cataracts. METHODS: Clinical data were collected, and the lens phenotypes of the affected members in this family were recorded by slit lamp photography. Genomic DNA was isolated from peripheral blood using QIAamp DNA Blood Mini Kits. Twenty-three mutational hot spots associated with autosomal dominant congenital posterior polar cataracts were screened by PCR-based DNA sequencing. Properties and structural models of wild-type and mutant alpha-B (?B)-crystallin (CRYAB) were generated and analyzed using SWISS-MODEL. RESULTS: All affected individuals in this family started to exhibit poor vision at the age of 8-10 years. The lens opacity consisted of a single, well-defined plaque, 0.5-3 mm in diameter, which was confined to the posterior pole of the lens. DNA sequencing analysis of the affected members showed a novel, heterozygous missense mutation c.59C?>?G (P20R) in exon 1 of the CRYAB gene. This mutation was not found in 10 unaffected family members, or in 200 unaffected and unrelated individuals, thereby excluding the possibility that it is a rare polymorphism. Data generated using the ProtScale and PyMOL programs revealed that the mutation altered the stability and solubility of the ?B-crystallin protein. CONCLUSIONS: This study reported a novel c.59C?>?G (P20R) missense mutation in CRYAB in a five-generation Chinese family with posterior polar cataract.

SUBMITTER: Xia XY

PROVIDER: S-EPMC4169818 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A novel P20R mutation in the alpha-B crystallin gene causes autosomal dominant congenital posterior polar cataracts in a Chinese family.

Xia Xin-Yi XY Wu Qiu-Yue QY An Li-Mei LM Li Wei-Wei WW Li Na N Li Tian-Fu TF Zhang Cui C Cui Ying-Xia YX Li Xiao-Jun XJ Xue Chun-Yan CY

BMC ophthalmology 20140908

<h4>Background</h4>To identify the genetic defects and investigate the possible mechanism of cataract genesis in a five-generation family with autosomal dominant congenital posterior polar cataracts.<h4>Methods</h4>Clinical data were collected, and the lens phenotypes of the affected members in this family were recorded by slit lamp photography. Genomic DNA was isolated from peripheral blood using QIAamp DNA Blood Mini Kits. Twenty-three mutational hot spots associated with autosomal dominant co ...[more]

PMID: 25195561

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Project description:Purpose:To identify mutations in crystallin genes in Chinese families with congenital cataracts. Methods:Forty-two unrelated families with non-syndromic congenital cataracts were enrolled in this study. The coding exons and adjacent intronic regions of crystallin genes, including CRYAA, CRYAB, CRYBA1, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGC, CRYGD and CRYGS, were analyzed with Sanger sequencing. Novel variants were further evaluated in 112 ethnically matched controls. To confirm the novel mutations, short tandem repeat (STR) haplotypes were constructed to check the cosegregation with congenital cataract. The pathogenic potential of the novel mutations were assessed using bioinformatics tools, including Sorting Intolerant From Tolerant v5.1.1 (SIFT), Polymorphism Phenotyping v2 (PolyPhen-2), and Human Splicing Finder. The pathogenicity of all the mutations was evaluated according to the guidelines of the American College of Medical Genetics (ACMG) and InterVar software. Results:Seven previously reported mutations in crystallin genes identified in ten unrelated families were associated with the congenital nuclear cataracts. Four novel mutations in crystallin genes, including c.35G>T (p.R12L) in CRYAA, c.463C>A (p.Q155K) in CRYBB2, IVS1 c.10-1G>A in CRYGC, and c.346delT (p.F116Sfsx29) in CRYGD, were identified in four unrelated families with congenital cataracts. These mutations cosegregated with all affected individuals in each family were not observed in the unaffected family members or in the 112 unrelated controls. All four novel mutations were categorized as disease "likely pathogenic" except IVS1 c.10-1G>A in CRYGC "pathogenic" using InterVar software in accordance with the ACMG standard. Mutations in crystallin genes were responsible for 33.33% of the Chinese families with congenital cataracts in this cohort. Conclusions:In this study, we identified four novel mutations in crystallin genes in Chinese families with congenital cataracts. The results expand the mutational spectrum of crystallin genes, which may be helpful for the molecular diagnosis of congenital cataracts in the era of precision medicine.

Dataset Information

A novel P20R mutation in the alpha-B crystallin gene causes autosomal dominant congenital posterior polar cataracts in a Chinese family.

Publications

A novel P20R mutation in the alpha-B crystallin gene causes autosomal dominant congenital posterior polar cataracts in a Chinese family.

Similar Datasets

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