From flies' eyes to our ears: Mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30
Genetic Markers
Male
0301 basic medicine
Genotype
Molecular Sequence Data
Deafness
Polymerase Chain Reaction
Cochlea
Pedigree
Mice
03 medical and health sciences
Mutation
Disease Progression
Animals
Drosophila
Female
Myosin Type III
Alleles
DNA Primers
Sequence Deletion
DOI:
10.1073/pnas.102091699
Publication Date:
2002-07-26T14:46:49Z
AUTHORS (10)
ABSTRACT
Normal vision in
Drosophila
requires NINAC, a class III myosin. Class III myosins are hybrid motor-signaling molecules, with an N-terminal kinase domain, highly conserved head and neck domains, and a class III-specific tail domain. In
Drosophila
rhabdomeres, NINAC interacts with actin filaments and with a PDZ scaffolding protein to organize the phototransduction machinery into a signaling complex. Recessive null mutations in
Drosophila
NINAC delay termination of the photoreceptor response and lead to progressive retinal degeneration. Here, we show that normal hearing in humans requires myosin IIIA, the human homolog of NINAC. In an extended Israeli family, nonsyndromic progressive hearing loss is caused by three different recessive, loss-of-function mutations in myosin IIIA. Of 18 affected relatives in Family N, 7 are homozygous and 11 are compound heterozygous for pairs of mutant alleles. Expression of mammalian myosin IIIA is highly restricted, with the strongest expression in retina and cochlea. The involvement of homologous class III myosins in both
Drosophila
vision and human hearing is an evolutionary link between these sensory systems.
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