Mutations of the unconventional
myosins genes encoding
myosin VI,
myosin VIIA and
myosin XV cause
hearing loss and thus these motor
proteins perform fundamental functions in the auditory system. A null mutation in
myosin VI in the congenitally deaf Snell's waltzer mice (Myo6(sv)) results in fusion of stereocilia and subsequent progressive loss of hair cells, beginning soon after birth, thus reinforcing the vital role of
cytoskeletal proteins in inner ear hair cells. To date, there are no human families segregating hereditary
hearing loss that show linkage to MYO6 on chromosome 6q13. The discovery that the mouse shaker1 (Myo7(ash1)) locus encodes
myosin VIIA led immediately to the identification of mutations in this gene in
Usher syndrome type 1B; subsequently, mutations in this gene were also found associated with recessive and dominant
nonsyndromic hearing loss (DFNB2 and
DFNA11). Stereocilla of sh1 mice are severely disorganized, and eventually degenerate as well.
Myosin VIIA has been implicated in membrane trafficking and/or endocytosis in the inner ear. Mutant alleles of a third unconventional
myosin,
myosin XV, are associated with nonsyndromic, recessive, congenital
deafness DFNB3 on human chromosome 17p11.2 and
deafness in shaker2 (Myo15(sh2)) mice. In outer and inner hair cells,
myosin XV
protein is detectable in the cell body and stereocilia. Hair cells are present in homozygous sh2 mutant mice, but the stereocilia are approximately 1/10 of the normal length. This review focuses on what we know about the molecular genetics and biochemistry of
myosins VI, VIIA and XV as relates to hereditary
hearing loss. Am. J. Med. Genet. (Semin. Med. Genet.) 89:147-157, 1999. Published 2000 Wiley-Liss, Inc.