Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal recessive cataract.

GJA8 encodes connexin-50, a gap junction protein in the eye lens. Mutations in GJA8 have been reported in families with autosomal dominant cataract. The objective of this report was to identify the disease gene in a family with congenital cataract of autosomal recessive inheritance. Eight candidate genes were screened for pathogenic alterations in affected and unaffected family members and in normal unrelated controls. A single base insertion leading to frameshift at codon 203 of connexin 50 was found to co-segregate with disease in the family. These results confirm involvement of GJA8 in autosomal recessive cataract.

A missense mutation in LIM2 causes autosomal recessive congenital cataract.

PURPOSE: To identify mutations in the LIM2 gene in families with hereditary congenital or juvenile-onset cataract. METHODS: Forty families (total of 100 affected and 84 unaffected individuals) were recruited for the study. Probands were screened for pathogenic alterations in 10 different candidate genes including the lens intrinsic membrane protein-2 (LIM2) gene. Exons and flanking regions were screened by polymerase chain reaction (PCR) amplification, single-strand conformation polymorphism, and sequencing. Sequence changes were evaluated in 75 unrelated normal controls. RESULTS: A missense mutation, Gly154Glu, was found in LIM2 in one family with four individuals diagnosed with autosomal recessive cataract from two generations. An evaluation of seven individuals (four affected and three unaffected) showed that the mutation was homozygous in the affected members and heterozygous in unaffected members tested. It was absent in 75 unrelated ethnically matched normal controls. All affected individuals had a severe phenotype of congenital cataracts and visual impairment. CONCLUSIONS: The Gly154Glu mutation involves a non-conservative change that presumably results in loss of function of the MP19 protein. This study shows the involvement of LIM2 in human congenital cataract.

Mutation of the gap junction protein alpha 8 (GJA8) gene causes autosomal recessive cataract.

BACKGROUND: GJA8 encodes connexin-50, a gap junction protein in the eye lens. Mutations in GJA8 have been reported in families with autosomal dominant cataract. OBJECTIVE: To identify the disease gene in a family with congenital cataract of autosomal recessive inheritance. METHODS: Eight candidate genes were screened for pathogenic alterations in affected and unaffected family members and in normal unrelated controls. RESULTS: A single base insertion leading to frameshift at codon 203 of connexin 50 was found to co-segregate with disease in the family. CONCLUSIONS: These results confirm involvement of GJA8 in autosomal recessive cataract.