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.
AQP0ΔC/ΔC lenses were transparent throughout the embryonic development and until postnatal day 15 (P15) in contrast to age-matched AQP0-/- lenses, which developed cataract at embryonic stage itself.
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.
Moreover, these observations predict that less severe defects in the AQP0 protein may contribute to lens opacity in patients with common, less fulminant forms of cataracts.
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.
We screened 60 known genes which are involved in inherited cataract in a pregnant woman with a four-generation family history of autosomal dominant congenital nuclear cataract through next-generation sequencing (NGS) and identified a heterozygous mutation, c.508dupC (p.L170fs), in the major intrinsic protein (MIP) gene.
Furthermore, this is the first clear evidence of allelic heterogeneity in this condition following the identification of a family with lamellar cataracts who have a different mutation within the MIP gene.
Overall, the Mip<sup>Nat</sup> mice offer a novel model to better understand the phenotypes and mechanisms for the development of cataracts in patients that carry missense mutations in MIP.
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.
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.
In summary, our study presented genetic and functional evidence linking the new MIP mutation of G215D to autosomal dominant congenital cataracts, which adds to the list of MIP mutations linked to congenital progressive punctate cataracts.
This study was aimed at exploring the potential pathogenesis of this mutation causative of cataract and mainly identifying how it influenced the binding of AQP0 to CaM.
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.
Sequence analysis of the major intrinsic protein of lens fiber gene (MIP), a gene known to cause other types of cataract in the linkage interval, detected a novel heterozygous initiation codon mutation, c.2T>C (p.Met1?).
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.