Localization of a novel gene for congenital nonsyndromic simple microphthalmia to chromosome 2q11-14

Microphthalmia is a clinically and genetically heterogeneous disorder of eye development. The genetic basis of nonsyndromic microphthalmia is not yet fully understood. Previous studies indicated that disease pedigrees from different genetic backgrounds could be attributed to completely different gene loci. To investigate the etiology in a large autosomal-dominant inherited simple microphthalmia (nanophthalmia) pedigree, which is the first genetically analyzed Chinese microphthalmia pedigree, we performed a whole-genome scan using 382 micro-satellite DNA markers after the exclusion of reported candidates associated with microphthalmia. Strong evidence indicated that microphthalmia in this family was mapped to an unreported new locus on chromosome 2q. A significantly positive two-point LOD score was obtained with a maximum 3.290 at a recombination fraction of 0.00 for marker D2S2265. Subsequent haplotype analysis and recombination data further confined the disease-causing gene to a 15-cM interval between D2S1890 and D2S347 on 2q11-14. Our results further underlined the degree of heterogeneity in microphthalmia from Chinese background and localized a novel gene which regulates eye embryogenesis.