The E368Q Mutant Allele of is Associated with Congenital Cataracts with Intrafamilial Variation in a South Indian Family.

PURPOSE

To determine the basis of the autosomal dominant congenital cataracts in a three generation south Indian pedigree.

METHODS

The proband and several family members underwent a complete ophthalmic examination. The coding regions of eight candidate genes ( and ) were amplified by PCR and directly sequenced. Wild type and mutant connexin50 (Cx50) were expressed by stable transfection of HeLa cells. Their cellular distributions and function were examined by immunofluorescence microscopy and by microinjection of gap junction permeant tracers, respectively.

RESULTS

Congenital cataracts (with some variations in phenotype) segregated as an autosomal dominant trait within a three generation pedigree. Three affected individuals (proband, sibling and mother) showed a sequence variation in the candidate gene encoding Cx50: a c.1102G>C transversion encoding a substitution of glutamate for glutamine at position 368 (E368Q). This substitution was absent from an unaffected family member (paternal aunt) and 100 healthy controls of the same ethnicity. In transfected HeLa cells, both wild type Cx50 and E368Q localized to gap junction plaques, and supported similar levels of intercellular transfer of Neurobiotin.

CONCLUSIONS

The E368Q mutant allele of is associated with autosomal dominant congenital cataracts with phenotypic variability. E368Q forms gap junction plaques and functional channels in transfected HeLa cells.