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.
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.
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.
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.
These results demonstrate that transgenic expression of Cx50 in mice leads to cataracts associated with formation of cytoplasmic vesicles containing Cx50 and decreased or slowed epithelial differentiation without major alterations in the distribution of other integral membrane or membrane-associated proteins or the integrity/solubility of crystallins.
Since the CPF is unique to nuclear cataract lenses, these data suggest that alpha-crystallin, and alpha B-crystallin in particular, may be implicated in the cataract process.
We studied the consequences of two cataract-associated mutations at adjacent positions at the first extracellular boundary in human connexin50 (Cx50), W45S and G46V.
To understand the mechanism of VP1-001, we tested the ability of its enantiomer, ent-VP1-001, to bind and stabilize αB-crystallin (cryAB) in vitro and to produce a similar therapeutic effect in cryAB(R120G) mutant and aged wild-type mice with cataracts.
Clinical characteristics of children with cataracts correlated with growth behavior of pLEC in vitro. mRNA expression of epithelial (αB-crystallin, connexin-43) and mesenchymal (αV-integrin, α-smooth muscle actin, collagen-Iα2, fibronectin-1) markers was quantified in pLEC and in cell line HLE-B3 in the presence and absence of TGFβ-2.
In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth.
To examine the mechanism by which a novel connexin 50 (Cx50) mutation, Cx50 V44A, in a Chinese family causes suture-sparing autosomal dominant congenital nuclear cataracts.
The results showed that GJA8 may participate in autophagy to maintain the intracellular environment, which may be a novel mechanism for cataract formation induced by GJA8.
The results show that in some individuals within one family, duplication of this segment of PITX3 can result in severe symptoms leading to functional blindness while in other individuals in the same family or in other families, the same duplication leads to treatable cataract with minimal visual impairment.
To screen for mutations of connexin50 (Cx50)/GJA8 in a panel of patients with inherited cataract and to determine the cellular and functional consequences of the identified mutation.