MYOSIN VIIA MUTATION SCREENING IN 189-USHER-SYNDROME TYPE-1 PATIENTS

Usher syndrome type 1b (USH1B) is an autosomal recessive disorder char acterized by congenital profound hearing loss, vestibular abnormalitie s, and retinitis pigmentosa, The disorder has recently been shown to b e caused by mutations in the myosin VIIa gene (MYO7A) located on 11q14 , In the current study, a panel of 189 genetically independent Usher I cases were screened for the presence of mutations in the N-terminal c oding portion of the motor domain of MYO7A by heteroduplex analysis of 14 exons, Twenty-three mutations were found segregating with the dise ase in 20 families, Of the 23 mutations, 13 were unique, and 2 of the 13 unique mutations (Arg212His and Arg212Cys) accounted for the greate st percentage of observed mutant alleles (8/23, 31%), Six of the 13 mu tations caused premature stop codons, 6 caused changes in the amino ac id sequence of the myosin VIIa protein, and 1 resulted in a splicing d efect, Three patients were homozygotes or compound heterozygotes for m utant alleles; these three cases were Tyr333Stop/Tyr333Stop, Arg212His -Arg302His/Arg212His-Arg302His, and IVS13nt-8c-->g/Glu450Gln. All the other USH1B mutations observed were simple heterozygotes, and it is pr esumed that the mutation on the other allele is present in the unscree ned regions of the gene, None of the mutations reported here were obse rved in 96 unrelated control samples, although several polymorphisms w ere detected, These results add three patients to single case reported previously where mutations have been found in both alleles and raises the total number of unique mutations in MYO7A to 16.