Genetic heterogeneity of Usher syndrome type II: localisation to chromosome 5q

Usher syndrome is a group of autosomal recessive disorders that includes re tinitis pigmentosa (RP) with hearing loss. Usher syndrome type II is define d as moderate to severe hearing loss with RP. The USH2A gene at 1q41 has be en isolated and characterised. In 1993, a large Usher II family affected wi th a mild form of RP was found to be unlinked to 1q41 markers. Subsequent l inkage studies of families in our Usher series identified several type II f amilies unlinked to USH2A and USH3 on 3q25. After a second unlinked family with many affected members and a mild retinal phenotype was discovered, a g enome search using these two large families showed another Usher II locus o n 5q (two point lod = 3.1 at D5S484). To date, we have identified nine unre lated 5q linked families (maximum combined multipoint lod = 5.86) as well a s three Usher II families that show no significant linkage to any known Ush er loci. Haplotype analysis of 5q markers indicates that the new locus is f lanked by D5S428 and D5S433. Review of ophthalmological data suggests that RP symptoms are milder in Sq linked families; the RP is often nor diagnosed until patients near their third decade. Enamel hypoplasia and severe, very early onset RP were observed in two of the three unlinked families; dental anomalies have not been previously described as a feature of Usher type II .