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Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts
- Source :
- Journal of Medical Genetics, Journal of Medical Genetics, BMJ Publishing Group, 2003
- Publication Year :
- 2003
- Publisher :
- BMJ Publishing Group, 2003.
-
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 gamma-crystallin gene (CRYG) cluster. Sequencing of the coding regions of the CRYGA, B, C, and D genes showed the presence of a heterozygous CA 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.
- Subjects :
- Male
Cerulean
DNA Mutational Analysis
Molecular Sequence Data
Mutation, Missense
Biology
bcs
Cataract
03 medical and health sciences
Exon
0302 clinical medicine
Crystallin
Genetics
medicine
Coding region
Humans
Amino Acid Sequence
gamma-Crystallins
[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Transversion
Gene
Genetics (clinical)
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Genes, Dominant
Family Health
0303 health sciences
Sequence Homology, Amino Acid
Haplotype
Chromosome Mapping
DNA
medicine.disease
eye diseases
Pedigree
Haplotypes
[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs
Chromosomes, Human, Pair 2
Mutation
030221 ophthalmology & optometry
Congenital cataracts
Female
Original Article
Lod Score
Microsatellite Repeats
Subjects
Details
- Language :
- English
- ISSN :
- 00222593 and 14686244
- Database :
- OpenAIRE
- Journal :
- Journal of Medical Genetics, Journal of Medical Genetics, BMJ Publishing Group, 2003
- Accession number :
- edsair.doi.dedup.....73b4b4b97812ed40e43bfa69458928a4