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Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene.
Invest Ophthalmol Vis Sci. 2004 Oct; 45(10):3599-607.IO

Abstract

PURPOSE

To study some functional candidate genes in cataract families of Indian descent.

METHODS

Nine Indian families, clinically documented to have congenital/childhood cataracts, were screened for mutations in candidate genes such as CRYG (A-->D), CRYBB2, and GJA8 by PCR analyses and sequencing. Genomic DNA samples of either probands or any representative affected member of each family were PCR amplified and sequenced commercially. Documentation of single nucleotide polymorphisms (SNPs) and candidate mutations was done through BLAST SEARCH (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi?).

RESULTS

Several single nucleotide polymorphisms in CRYG, CRYBB2, and GJA8 genes were observed. Because they do not co-segregate with the phenotype, they were excluded as candidates for the cataract formation in these patients. However, a substitution (W151C in exon 6 of CRYBB2) was identified as the most likely causative mutation underlying the phenotype of central nuclear cataract in all affected members of family C176. Protein structural interpretations demonstrated that no major structural alterations could be predicted and that even the hydrogen bonds to the neighboring Leu166 were unchanged. Surprisingly, hydropathy analysis of the mutant betaB2-crystallin featuring the amino acids at position 147 to 155, further increased the hydrophobicity, which might impair the solubility of the mutant protein. Finally, the Cys residue at position 151 might possibly be involved in intramolecular disulphide bridges with other cysteines during translation, possibly leading to dramatic structural changes.

CONCLUSIONS

Exon 6 of CRYBB2 appears to be a critical region susceptible for mutations leading to lens opacity.

Authors+Show Affiliations

Dr. ALM Postgraduate Institute of Basic Medical Sciences, Department of Genetics, University of Madras, Taramani, Chennai, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15452067

Citation

Santhiya, Sathiyavedu T., et al. "Mutation Analysis of Congenital Cataracts in Indian Families: Identification of SNPS and a New Causative Allele in CRYBB2 Gene." Investigative Ophthalmology & Visual Science, vol. 45, no. 10, 2004, pp. 3599-607.
Santhiya ST, Manisastry SM, Rawlley D, et al. Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene. Invest Ophthalmol Vis Sci. 2004;45(10):3599-607.
Santhiya, S. T., Manisastry, S. M., Rawlley, D., Malathi, R., Anishetty, S., Gopinath, P. M., Vijayalakshmi, P., Namperumalsamy, P., Adamski, J., & Graw, J. (2004). Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene. Investigative Ophthalmology & Visual Science, 45(10), 3599-607.
Santhiya ST, et al. Mutation Analysis of Congenital Cataracts in Indian Families: Identification of SNPS and a New Causative Allele in CRYBB2 Gene. Invest Ophthalmol Vis Sci. 2004;45(10):3599-607. PubMed PMID: 15452067.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mutation analysis of congenital cataracts in Indian families: identification of SNPS and a new causative allele in CRYBB2 gene. AU - Santhiya,Sathiyavedu T, AU - Manisastry,Shyam Manohar, AU - Rawlley,Deepika, AU - Malathi,Raghunathan, AU - Anishetty,Sharmila, AU - Gopinath,Puthiya M, AU - Vijayalakshmi,Perumalsamy, AU - Namperumalsamy,Perumalsamy, AU - Adamski,Jerzy, AU - Graw,Jochen, PY - 2004/9/29/pubmed PY - 2004/11/9/medline PY - 2004/9/29/entrez SP - 3599 EP - 607 JF - Investigative ophthalmology & visual science JO - Invest. Ophthalmol. Vis. Sci. VL - 45 IS - 10 N2 - PURPOSE: To study some functional candidate genes in cataract families of Indian descent. METHODS: Nine Indian families, clinically documented to have congenital/childhood cataracts, were screened for mutations in candidate genes such as CRYG (A-->D), CRYBB2, and GJA8 by PCR analyses and sequencing. Genomic DNA samples of either probands or any representative affected member of each family were PCR amplified and sequenced commercially. Documentation of single nucleotide polymorphisms (SNPs) and candidate mutations was done through BLAST SEARCH (http://www.ncbi.nlm.nih.gov/blast/Blast.cgi?). RESULTS: Several single nucleotide polymorphisms in CRYG, CRYBB2, and GJA8 genes were observed. Because they do not co-segregate with the phenotype, they were excluded as candidates for the cataract formation in these patients. However, a substitution (W151C in exon 6 of CRYBB2) was identified as the most likely causative mutation underlying the phenotype of central nuclear cataract in all affected members of family C176. Protein structural interpretations demonstrated that no major structural alterations could be predicted and that even the hydrogen bonds to the neighboring Leu166 were unchanged. Surprisingly, hydropathy analysis of the mutant betaB2-crystallin featuring the amino acids at position 147 to 155, further increased the hydrophobicity, which might impair the solubility of the mutant protein. Finally, the Cys residue at position 151 might possibly be involved in intramolecular disulphide bridges with other cysteines during translation, possibly leading to dramatic structural changes. CONCLUSIONS: Exon 6 of CRYBB2 appears to be a critical region susceptible for mutations leading to lens opacity. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/15452067/Mutation_analysis_of_congenital_cataracts_in_Indian_families:_identification_of_SNPS_and_a_new_causative_allele_in_CRYBB2_gene_ L2 - http://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.04-0207 DB - PRIME DP - Unbound Medicine ER -