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* Departments of Medicine and Genome Sciences, University of
Washington, Seattle, WA 98195-7720; Edited by A. James Hudspeth, The Rockefeller University, New
York, NY, and approved March 22, 2002 (received for review February 13, 2002)
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.
Genetics
From flies' eyes to our ears: Mutations in a human class III
myosin cause progressive nonsyndromic hearing loss DFNB30
,,,
,,,
Department of Human
Genetics and Molecular Medicine, Sackler School of Medicine, Tel
Aviv University, Tel Aviv 69978, Israel; and Department
of Life Sciences, Bethlehem University, Bethlehem, Palestinian
Authority
§
To whom reprint requests should be addressed. E-mail:
mcking{at}u.washington.edu.
www.pnas.org/cgi/doi/10.1073/pnas.102091699
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