Microphthalmia, Isolated, With Coloboma 2

For a discussion of genetic heterogeneity of isolated colobomatous microphthalmia, see MCOPCB1 (300345).

Clinical Features

Morle et al. (2000) studied a 5-generation Sephardic Jewish family in which 7 of 38 members had either unilateral or bilateral microphthalmia of variable severity inherited as an autosomal dominant trait with incomplete penetrance. The inclusion criterion for the diagnosis of microphthalmia was reduction of the total axial length to less than 20 mm in at least 1 eye, determined by ultrasonography. Five of the 7 affected individuals had an ocular prosthesis in at least 1 eye. Two individuals were of uncertain status, since they had ocular anomalies but normal axial length bilaterally. The incomplete penetrance and variable expression was illustrated by an individual who had corneal clouding and iridocorneal synechia (Peters anomaly) but no microphthalmia, and by 2 individuals with unilateral optic nerve agenesis associated with coloboma of the iris and of the retina, respectively.

Mapping

By linkage studies in a 5-generation Sephardic Jewish family with microphthalmia and other eye anomalies, Morle et al. (2000) excluded 7 candidate genes. By a genome scan, they demonstrated linkage of the disorder in this family to chromosome 15q12-q15. A maximum lod score of 3.77 was obtained for linkage to D15S1007, at a recombination fraction of 0.00. Haplotype analyses narrowed the assignment to a 13.8-cM interval.

Michon et al. (2004) performed linkage analysis in the 5-generation Sephardic Jewish family previously reported by Morle et al. (2000) and refined the disease locus to 2 intervals in close proximity, a 1.9-Mb centromeric interval bounded by microsatellite DNA markers m3 and m17 and a 2.5-Mb telomeric interval bounded by m76 and m24. The authors excluded 3 candidate genes. Although a phenomenon of anticipation was suggested by phenotypic and pedigree data, no abnormal expansion of 3 trinucleotide repeats mapping to the refined interval was found in affected individuals.