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A novel gammaD-crystallin mutation causes mild changes in protein properties but leads to congenital coralliform cataract.

ABSTRACT: PURPOSE: To identify the genetic lesions for congenital coralliform cataract. METHODS: Two Chinese families with autosomal dominant coralliform cataract, 12 affected and 14 unaffected individuals, were recruited. Fifteen known genes associated with autosomal dominant congenital cataract were screened by two-point linkage analysis with gene based single nucleotide polymorphisms and microsatellite markers. Sequence variations were identified. Recombinant FLAG-tagged wild type or mutant gammaD-crystallin was expressed in human lens epithelial cells and COS-7 cells. Protein solubility and intracellular distribution were analyzed by western blotting and immunofluorescence, respectively. RESULTS: A novel heterozygous change, c.43C>A (R15S) of gammaD-crystallin (CRYGD) co-segregated with coralliform cataract in one family and a known substitution, c.70C>A (P24T), in the other family. Unaffected family members and 103 unrelated control subjects did not carry these mutations. Similar to the wild type protein, R15S gammaD-crystallin was detergent soluble and was located in the cytoplasm. ProtScale and ScanProsite analyses revealed raised local hydrophobicity and the creation of a hypothetical casein kinase II phosphorylation site. CONCLUSIONS: A novel R15S mutation caused congenital coralliform cataract in a Chinese family. R15S possessed similar properties to the wild type gammaD-crystallin, but its predicted increase of hydrophobicity and putative phosphorylation site could lead to protein aggregation, subsequently causing opacification in lens.

SUBMITTER: Zhang LY

PROVIDER: S-EPMC2722711 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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A novel gammaD-crystallin mutation causes mild changes in protein properties but leads to congenital coralliform cataract.

Zhang Li-Yun LY Gong Bo B Tong Jian-Ping JP Fan Dorothy Shu-Ping DS Chiang Sylvia Wai-Yee SW Lou Dinghua D Lam Dennis Shun-Chiu DS Yam Gary Hin-Fai GH Pang Chi-Pui CP

Molecular vision 20090806

<h4>Purpose</h4>To identify the genetic lesions for congenital coralliform cataract.<h4>Methods</h4>Two Chinese families with autosomal dominant coralliform cataract, 12 affected and 14 unaffected individuals, were recruited. Fifteen known genes associated with autosomal dominant congenital cataract were screened by two-point linkage analysis with gene based single nucleotide polymorphisms and microsatellite markers. Sequence variations were identified. Recombinant FLAG-tagged wild type or mutan ...[more]

PMID: 19668596

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Project description:BackgroundCongenital cataract is a leading cause of treatable childhood blindness and both clinically and genetically heterogeneous. Among the already characterized phenotypes, coralliform cataract is a rare special form of congenital cataracts. Although previous studies had shown that mutations in the γD-crystallin (CRYGD) can result in congenital coralliform cataracts, no conclusive genotype-phenotype correlation might be drawn. Here we aimed to identify the spectrum and frequency of CRYGD gene mutations in congenital coralliform cataracts of Chinese origin.MethodsThe medical records of 392 Chinese families with congenital cataracts were reviewed between January 2011 and December 2021. The families, clinically documented to have congenital coralliform cataracts, were screened for mutations in candidate CRYGD gene. The genomic DNA of all subjects was extracted from peripheral blood leukocytes. PCR amplified and direct sequencing were performed to identify the disease-causing mutation.ResultsA total of 12 families with coralliform cataracts were recruited in this study in the past 10 years, accounting for 3.1% of the families with congenital cataracts. Of the 12 families, all affected individuals presented with bilateral non-progressive coralliform cataracts since birth, with the best-corrected Snellen visual acuities ranging from 20/200 to 20/25. A recurrent c.70 C > A (p. P24T) mutation in CRYGD was identified in 10 families (83.3%) with congenital cataract, which co-segregated with all affected individuals and was not observed in unaffected family members or ethnically matched normal controls.ConclusionsThe coralliform cataract is characterized by being bilateral, non-progressive and present at birth. A recurrent p.P24T CRYGD mutation occurs independently in 83.3% of the Chinese families with congenital coralliform cataracts and most likely represents a mutational hot spot, which underscore the relations between coralliform cataract and p.P24T CRYGD.

Dataset Information

A novel gammaD-crystallin mutation causes mild changes in protein properties but leads to congenital coralliform cataract.

Publications

A novel gammaD-crystallin mutation causes mild changes in protein properties but leads to congenital coralliform cataract.

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