MYOSIN VIIA GENE - HETEROGENEITY OF THE MUTATIONS RESPONSIBLE FOR USHER-SYNDROME TYPE IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural dea fness, constant vestibular dysfunction, and retinitis pigmentosa of pr epubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1B (which accounts for similar to 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequ ence were designed, allowing direct sequence analysis of each of the 4 8 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified.,The possibility s hould now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.