PURPOSE To identify the underlying genetic defect in a three-generation family with five members affected with dominant bilateral congenital cataract and microcornea. METHODS Detailed family history and clinical data were recorded. Mutation screening in the candidate genes, CRYAA, CRYBB1, MAF, GJA3, and GJA8, was performed by bidirectional sequencing of the amplified products. RESULTS Affec...

PURPOSE To characterize the disease-causing mutations in four generations of a Chinese family affected with bilateral congenital nuclear and zonular pulverulent cataract. METHODS Detailed family history and clinical data were recorded. The phenotype was documented using slit-lamp photography. Candidate genes were amplified using PCR and screened for mutations using bidirectional sequencing. ...

PURPOSE We isolated an autosomal semi-dominant cataract from our inbred SHR/OlaIpcv rat colony. Heterozygotes express pulverulent cataract with smaller eyes; homozygotes express marked microphthalmia with hypoplastic lens. We call this mutation Dca (for dominant cataract). In this study, we focus on the identification of the responsible gene. METHODS We performed linkage mapping using 93 F2(S...

PURPOSE To study some functional candidate genes in cataract families of Indian descent. METHODS Nine Indian families, clinically documented to have congenital/childhood cataracts, were screened for mutations in candidate genes such as CRYG (A-->D), CRYBB2, and GJA8 by PCR analyses and sequencing. Genomic DNA samples of either probands or any representative affected member of each family were...

We assessed the effect of the previously uncovered gap junction protein alpha 8 (Gja8) mutation present in spontaneously hypertensive rat - dominant cataract (SHR-Dca) strain on blood pressure, metabolic profile, and heart and renal transcriptomes. Adult, standard chow-fed male rats of SHR and SHR-Dca strains were used. We found a significant, consistent 10-15 mmHg decrease in both systolic and...

A unique sutural cataract was observed in a 4-generation German family to be transmitted as an isolated autosomal, dominant trait. Since mutations in the gamma-crystallin encoding CRYG genes have previously been demonstrated to be the most frequent reason for isolated congenital cataracts, all 4 active CRYG genes have been sequenced. A single base-pair change in the CRYGA gene has been shown, l...

Different mutations of alpha3 connexin (Cx46 or Gja8) and alpha8 connexin (Cx50 or Gja8), subunits of lens gap junction channels, cause a variety of cataracts via unknown mechanisms. We identified a dominant cataractous mouse line (L1), caused by a missense alpha8 connexin mutation that resulted in the expression of alpha8-S50P mutant proteins. Histology studies showed that primary lens fiber c...

PURPOSE The roles of gap junction protein connexin 50 (Cx50) encoded by Gja8, during lens development are not fully understood. Connexin 50 knockout (KO) lenses have decreased proliferation of epithelial cells and altered fiber cell denucleation. We further investigated the mechanism for cellular defects in Cx50 KO (Gja8-/-) lenses. METHODS Fiber cell morphology and subcellular distribution o...