HUMAN MYOSIN VIIA RESPONSIBLE FOR THE USHER 1B SYNDROME - A PREDICTEDMEMBRANE-ASSOCIATED MOTOR PROTEIN EXPRESSED IN DEVELOPING SENSORY EPITHELIA

The gene encoding human myosin VIIA is responsible for Usher syndrome type 1B (USH1B), a disease which associates profound congenital sensor ineural deafness, vestibular dysfunction, and retinitis pigmentosa, Th e reconstituted cDNA sequence presented here predicts a 2215 amino aci d protein with a typical unconventional myosin structure, This protein is expected to dimerize into a two-headed molecule, The C terminus of its tail shares homology with the membrane-binding domain of the band 4.1 protein superfamily, The gene consists of 48 coding exons, It enc odes several alternatively spliced forms, In situ hybridization analys is in human embryos demonstrates that the myosin VIIA gene is expresse d in the pigment epithelium and the photoreceptor cells of the retina, thus indicating that both cell types may be involved in the USH1B ret inal degenerative process, In addition, the gene is expressed in the h uman embryonic cochlear and vestibular neuroepithelia, We suggest that deafness and vestibular dysfunction in USH1B patients result from a d efect in the morphogenesis of the inner ear sensory cell stereocilia.