Nandrot, E. and Slingsby, Christine and Basak, Ajit K. and Cherif Chefchaouni, M. and Benazzouz, B. and Hajaji, Y. and Boutayeb, S. and Gribouval, O. and Arbogast, L. and Berraho, A. and Abitbol, M. and Hilal, L. (2003) Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts. Journal of Medical Genetics 40 (4), pp. 262-267. ISSN 0022-2593.
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Abstract
Congenital cataracts are a major cause of bilateral visual impairment in childhood. We mapped the gene responsible for autosomal congenital cerulean cataracts to chromosome 2q33-35 in a four generation family of Moroccan descent. The maximum lod score (7.19 at recombination fraction theta=0) was obtained for marker D2S2208 near the g-crystallin gene (CRYG) cluster. Sequencing of the coding regions of the CRYGA, B, C, and D genes showed the presence of a heterozygous C>A transversion in exon 2 of CRYGD that is associated with cataracts in this family. This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterise this protein. We show that although the x ray crystallography modelling does not indicate any change of the backbone conformation, the mutation affects a region of the Greek key motif that is important for determining the topology of this protein fold. Our data suggest strongly that the proline to threonine substitution may alter the protein folding or decrease the thermodynamic stability or solubility of the protein. Furthermore, this is the first report of a mutation in this gene resulting in autosomal dominant congenital cerulean cataracts.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | ZONULAR PULVERULENT CATARACT, EYE LENS, JUVENILE-ONSET, HEREDITARY CATARACT, CHROMOSOME 2Q33-35, MISSENSE MUTATION, POLAR CATARACT, FAMILY, PROTEINS, LINKAGE |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 14 Feb 2005 |
| Last Modified: | 02 Aug 2023 16:45 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/78 |
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