GENETIC-HETEROGENEITY OF USHER SYNDROME TYPE-II

Usher syndrome is an autosomal recessive disorder characterised by ret initis pigmentosa and congenital sensorineural hearing loss. A gene fo r Usher syndrome type II (USH2) has been localised to chromosome 1q32- q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which a re believed to flank USH2. Genotypic results and subsequent linkage an alysis indicated non-linkage of this family to these markers. The A te st analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p<0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences w ere observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Us her syndrome genes using linkage analysis and limits the use of DNA ma rkers in early detection of Usher type II.