Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditarydeaf-blindness. Usher syndrome type I (USH1), the most severe form of thedisease, is characterized by profound congenital sensorineural deafness,constant vestibular dysfunction, and retinitis pigmentosa of prepubertalonset. This form is genetically heterogeneous and five loci (USH1A-E) havebeen mapped thusfar. However, only the gene responsible for USH1 B (whichaccounts for approximately 75% of USH1 cases) has been characterized. Itencodes a long-tailed unconventional myosin, myosin VIIA, with a predicted2215 amino acid sequence. Primers covering the complete myosin VIIA codingsequence as well as the 3' non coding sequence were designed, allowingdirect sequence analysis of each of the 48 coding exons and flanking splicesites in seven patients affected by USH1. Four novel mutations were therebyidentified. The possibility should now be considered of a sequence-basedprenatal diagnosis in some of the families affected by this very severeform of Usher syndrome.