A new lead to understanding normal eye development has emerged from a molecular genetic study mapping the disease locus of a rare complex optical syndrome to a region within the locus for nanophthalmia

The study was confined to three generations of one English family, six of whom were affected with an autosomal dominant condition (MRCS) in which microcornea, progressive rod-cone dystrophy, cataract and posterior staphyloma segregate together.

The affected phenotype was consistent with nanophthalmia, plus other characteristics and suggested that the disease locus might occur on chromosome 11. Genetic testing with microsatellite markers associated with autosomal dominant nanophthalmia excluded CMIC and CHX10 loci on chromosome 14q and NNO2 on chromosome 15, but linkage results suggested a 5.0 cM genetic interval within the NNO1 locus as the most likely site.

Six affected members and three unaffected members of one family were tested from 11 members who agreed to participate. Each had comprehensive medical and ophthalmological examinations and gave venous blood for DNA amplification and genotyping with microsatellite markers associated with nanophthalmia by a positional candidate gene approach.

Autosomal dominant nanophthalmia has been assigned a locus at NNO1 between chromosome 11p12 and 11q13 by a previous linkage study in one family. So it seemed a useful candidate to test for mutation in a family with autosomal dominant MRCS. The researchers are seeking to confirm their results by testing more affected families and to screen for other candidate genes in this region.