Human γd-crystallin (Hγd-crystallin), a major protein component of the human eye lens, is associated with the development of juvenile- and mature-onset cataracts.
Mutational analysis of CRYGD identified a recurrent (p.P24T) mutation in two unrelated families with congenital coralliform cataracts and three novel (p.Q101X, p.E104fsX4 and p.E135X) mutations in three families with congenital nuclear cataracts.
Some mutants of human γD-crystallin are closely linked to congenital cataracts, although the detailed molecular mechanisms of mutant-associated cataract formation are generally not known.
Interestingly, a mutation of different codon, i.e., p.Arg58His in CRYGD has been reported to be linked with aculeiform cataract in four different families; two from Switzerland, one from Macedonia and in a Mexican family.
Although a number of γD-crystallin mutations are associated with cataract formation, there is not a clear understanding of the molecular mechanism(s) that lead to this protein deposition disease.
Benedek, J. Pande, Decrease in protein solubility and cataract formation caused by the Pro23 to Thr mutation in human gamma D-crystallin, Biochemistry 44 (2005) 2491-2500] that the mutation dramatically lowers the solubility of P23T but the overall protein fold is maintained.
Direct sequencing of the candidate CRYGA-CRYGD gene cluster revealed a c.470G>A transversion in exon 3 of CRYGC, which cosegregated with cataracts in the family and was not observed in 100 normal controls.
The cataract-associated serine at site 23 corresponds to the ancestral state, since it was found in CRYGD of a lower primate and all the surveyed nonprimate mammals.
To present a previously unreported four generation affected Mexican pedigree with congenital hereditary aculeiform cataract caused by a mutation in the gammaD-crystallin (CRYGD) gene.
It appeared to be caused by a missense mutation in the CRYGD gene, further supporting the notion that alterations to CRYG play an important factor in human cataract formation.
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.
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.