A Mutation of PCDH15 among Ashkenazi Jews with the Type 1 Usher Syndrome

Abstract

The usher syndrome is an autosomal recessive disorder char- acterized by bilateral sensorineural deafness and progressive loss of vision due to retinitis pigmentosa. It is the most frequent cause of deafness and con- current blindness, 1 with a prevalence of 1 in 16,000 to 1 in 50,000. 2 The majority of cas- es of the Usher syndrome can be classified into one of three clinical subtypes, the most severe of which is the type 1 Usher syndrome, characterized by profound prelingual hearing loss, vestibular areflexia, and prepubertal onset of retinitis pigmentosa. 2 Seven loci for the type 1 Usher syndrome ( USH1A to USH1G ) have been mapped to distinct chromosomal regions by genetic-linkage studies, 2,3 and the causative genes have been identified for five of them. 4-10 Several rare genetic disorders in Ashkenazi Jews are associated with prevalent founder mutations segregating in this population. 11-15 A reduction in the incidence of such dis- orders is possible through effective genetic education, screening, and counseling. We previously identified a founder mutation in the GJB2 gene, 167delT, which is carried by 4 percent of Ashkenazi Jews and is one of the major causes of autosomal recessive non- syndromic hearing loss in this population. 16 We hypothesized that, similarly, at least one founder mutation that arose in an ancestral Ashkenazi Jew is a prevalent cause of the type 1 Usher syndrome in the current population. methods