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.

• Authors: Li-Yun Zhang, Bo Gong, Jian-Ping Tong, Dorothy Shu-Ping Fan, Sylvia Wai-Yee Chiang, Dinghua Lou, Dennis Shun-Chiu Lam, Gary Hin-Fai Yam, Chi-Pui Pang
• Journal: Molecular vision (Mol Vis) Vol. 15 Pg. 1521-9 (Aug 06 2009) ISSN: 1090-0535 [Electronic] United States
• PMID: 19668596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CRYGD protein, human
• Mutant Proteins
• gamma-Crystallins
• Serine
• Arginine

Topics

• Adult
• Amino Acid Sequence
• Arginine (genetics)
• Asian People
• Base Sequence
• Cataract (congenital, genetics)
• Child
• Child, Preschool
• Computational Biology
• DNA Mutational Analysis
• Family
• Female
• Genetic Linkage
• Humans
• Hydrophobic and Hydrophilic Interactions
• Infant
• Male
• Molecular Sequence Data
• Mutant Proteins (chemistry, genetics)
• Mutation (genetics)
• Organ Specificity
• Pedigree
• Protein Transport
• Serine (genetics)
• Solubility
• gamma-Crystallins (chemistry, genetics, metabolism)