THE AUTOSOMAL RECESSIVE ISOLATED DEAFNESS, DFNB2, AND THE USHER 1B SYNDROME ARE ALLELIC DEFECTS OF THE MYOSIN-VIIA GENE

Hereditary non-syndromic profound deafness affects about 1 in 2000 chi ldren prior to language acquisition. In 80% of the cases, the mode of transmission is autosomal recessive. The number of genes involved in t hese recessive forms of isolated deafness (DFNB genes) has been estima ted to between 30 and 100. So far, ten DFNB genes have been mapped to human chromosomes, one of which has been isolated(2). By linkage analy sis of a single family whose members were affected with profound deafn ess, some of them presenting with vestibular dysfunction, DFNB2 has be en mapped to chromosome 11q13 (ref. 3), The gene responsible for a for m of Usher syndrome type I, USH1B, has been assigned to the same chrom osomal region(4). Usher syndrome associates profound congenital deafne ss and vestibular dysfunction with retinitis pigmentosa. In the homolo gous murine region are located the shaker-1 mutations responsible for deafness and vestibular dysfunction. It has been demonstrated that the murine shaker-1 and human USH1B phenotypes result from mutations in t he gene encoding myosin-VIIA(5,6). Based on mapping data as well as on the similarities between the phenotypes of DFNB2-affected patients an d shaker-1 mouse mutants, we have proposed that a defective myosin-VII A may also be responsible for DFNB2 (ref. 1). Sequence analysis of eac h of the coding exons of the myosin-VIIA gene (MYO7A) was thus underta ken in the DFNB2-affected family. In the last nucleotide of exon 15, a G to A transition was detected, a type of mutation that is known to d ecrease the efficiency of splicing(7-14). Accordingly, this result sho ws that different mutations in MYO7A result in either an isolated or a syndromic form of deafness.