A Novel Dominantly Inherited Congenital Cataract, Microcornea, Microphthalmia and Atypical Iris Coloboma Is Linked to Chromosome 2q

Abstract

Purpose:: To characterize a novel phenotype of autosomal dominant congenital cataract associated with microcornea, variable expression of microphthalmia and iris coloboma affecting a large family, and to identify the locus linked to this new syndrome.

Methods:: An Egyptian family of four generations with twenty-four affected members was examined. Family history and clinical data were recorded. Phenotype was documented by slit lamp, axial length measurement and fundus photographs. DNA was extracted from blood samples of affected patients. Genome-wide linkage analysis was performed and lod-scores were calculated with autoscan.

Results:: A novel form of hexagonal nuclear cataract with cortical riders was expressed in some patients, while different morphologies such as anterior polar and zonular extension were seen in others. Ninety-two percent of the affected had microcornea and sixty-one percent had microphthalmia. Five affected patients presented an additional feature consisting of an atypical iris coloboma. Linkage was observed on chromosome 2 for DNA marker D2S2358 (lod score: 4.03 at θ = 0). Individual V-7 recombined at marker D2S117 and individuals V-18 and V-19 at marker D2S2242 thus defining a common haplotype of 13.3 cM.

Conclusions:: We have identified a new locus on chromosome 2 flanked by markers D2S117 and D2S2242. This locus is linked to a new autosomal dominant syndrome composed of a novel "hexagonal" cataract phenotype with microcornea and additional microphthalmia and/or atypical iris coloboma. We are unaware of previous reports of this association. Additional families with a similar phenotype are being investigated in order to reduce the linked interval and candidate genes are being screened.

Keywords: cataract • gene mapping • anterior segment