Dataset Information

Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts.

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 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.

SUBMITTER: Nandrot E

PROVIDER: S-EPMC1735438 | biostudies-other | 2003 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts.

Nandrot E E Slingsby C C Basak A A Cherif-Chefchaouni M M Benazzouz B B Hajaji Y Y Boutayeb S S Gribouval O O Arbogast L L Berraho A A Abitbol M M Hilal L L

Journal of medical genetics 20030401 4

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 C>A transversion in exon ...[more]

PMID: 12676897

Similar Datasets

Project description:PURPOSE: To identify the underlying genetic defect in a north Indian family with seven members in three-generations affected with bilateral congenital cataract. METHODS: Detailed family history and clinical data were recorded. Linkage analysis using fluorescently labeled microsatellite markers for the already known candidate gene loci was performed in combination with mutation screening by bidirectional sequencing. RESULTS: Affected individuals had bilateral congenital cataract. Cataract was of opalescent type with the central nuclear region denser than the periphery. Linkage was excluded for the known cataract candidate gene loci at 1p34-36, 1q21-25 (gap junction protein, alpha 8 [GJA8]), 2q33-36 (crystallin, gamma A [CRYGA], crystallin, gamma B [CRYGB], crystallin, gamma C [CRYGC], crystallin, gamma D [CRYGD], crystallin, beta A2 [CRYBA2]), 3q21-22 (beaded filament structural protein 2, phakinin [BFSP2]), 12q12-14 (aquaporin 0 [AQP0]), 13q11-13 (gap junction protein, alpha 3 [GJA3]), 15q21-22, 16q22-23 (v-maf musculoaponeurotic fibrosarcoma oncogene homolog [MAF], heat shock transcription factor 4 [HSF4]), 17q11-12 (crystallin, beta A1 [CRYBA1]), 17q24, 21q22.3 (crystallin, alpha A [CRYAA]), and 22q11.2 (crystallin, beta B1 [CRYBB1], crystallin, beta B2 [CRYBB2], crystallin, beta B3 [CRYBB3], crystallin, beta A4 [CRYBA4]). Crystallin, alpha B (CRYAB) at chromosome 11q23-24 was excluded by sequence analysis. However, sequencing the candidate gene, crystallin, gamma S (CRYGS), at chromosome 3q26.3-qter showed a heterozygous c.176G-->A change that resulted in the replacement of a structurally highly conserved valine by methionine at codon 42 (p.V42M). This sequence change was not observed in unaffected family members or in the 100 ethnically matched controls. CONCLUSIONS: We report a novel missense mutation, p.V42M, in CRYGS associated with bilateral congenital cataract in a family of Indian origin. This is the third report of a mutation in this exceptional member of the beta-/gamma-crystallin superfamily and further substantiates the genetic and clinical heterogeneity of autosomal dominant cataract.

Dataset Information

Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts.

Publications

Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets