From flies' eyes to our ears: Mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30

• DOI: 10.1073/pnas.102091699
• Publication Date: 2002-07-26T14:46:49Z
• Authors: Tom Walsh; Vanessa Walsh; Sarah Vreugde; Ronna Hertzano; Hashem Shahin; Smadar Haika; Ming K. Lee; Moien Kanaan; Mary-Claire King; Karen B. Avraham
• Keywords: Null allele; Visual phototransduction; PDZ domain

Normal vision in Drosophila requires NINAC, a class III myosin. Class myosins are hybrid motor-signaling molecules, with an N-terminal kinase domain, highly conserved head and neck domains, III-specific tail domain. In rhabdomeres, NINAC interacts actin filaments PDZ scaffolding protein to organize the phototransduction machinery into signaling complex. Recessive null mutations delay termination of photoreceptor response lead progressive retinal degeneration. Here, we show that normal hearing humans myosin IIIA, human homolog NINAC. extended Israeli family, nonsyndromic loss is caused by three different recessive, loss-of-function IIIA. Of 18 affected relatives Family N, 7 homozygous 11 compound heterozygous for pairs mutant alleles. Expression mammalian IIIA restricted, strongest expression retina cochlea. The involvement homologous both evolutionary link between these sensory systems.