Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tremendous progress has been made in our understanding of the molecular basis of hearing and hearing loss. Through recent advances, we have begun to understand the fascinating biology of the auditory system and unveiled new molecular mechanisms of hearing impairment. Changes in the diagnostic impact of genetic testing have occurred, as well as exciting developments in therapeutic options. Molecular diagnosis, which is already a reality for several hearing-associated genes, will doubtlessly continue to increase in the near future, both in terms of the number of mutations tested and the spectrum of genes. Genetic analysis for hearing loss is mostly used for diagnosis and treatment, and relatively rarely for reproductive decisions, in contrast to other inherited disorders. Inherited hearing loss, however, is characterized by impressive genetic heterogeneity. An abundance of genes carry a large number of mutations, but specific mutations in a single gene may lead to syndromic or non-syndromic hearing loss. Some mutations predominate in individual ethnic groups. For clinical and laboratory diagnosticians, it is challenging to keep abreast of the unfolding discoveries. This review aims to provide the framework pertinent to diagnosticians and a practical approach to mutation analysis in the hearing impaired.
J Mol Diagn 2004 Nov
PMID:Hereditary non-syndromic sensorineural hearing loss: transforming silence to sound. 1550 65

Inherited hearing loss in mice has contributed substantially to our understanding of inner-ear function. We identified a new allele at the Myo7a locus, Myo7a(sh1-8J); genomic characterization indicated that Myo7a(sh1-8J) arose from complex deletion encompassing exons 38-40 and 42-46. Homozygous mutant mice had no detectable auditory brainstem response, displayed highly disorganized hair-cell stereocilia and had no detectable MYO7A protein. We generated mice that were digenic heterozygotes for Myo7a(sh1-8J) and one of each Cdh23(v-2J), Ush1g(js) or Pcdh15(av-3J) alleles, or an Ush1c null allele. Significant levels of age-related hearing loss were detected in +/Myo7a(sh1-8J) +/Ush1g(js), +/Myo7a(sh1-8J) +/Cdh23(v-2J) and +/Myo7a(sh1-8J) +/Pcdh15(av-3J) double heterozygous mice compared with age-matched single heterozygous animals, suggesting epistasis between Myo7a and each of the three loci. +/Pcdh15(av-3J) +/Ush1g(js) double heterozygous mice also showed elevated hearing loss, suggesting Pcdh15-Ush1g epistasis. While we readily detected MYO7A, USH1C, CDH23 and PCDH15 using mass spectrometry of purified chick utricle hair bundles, we did not detect USH1G. Consistent with that observation, Ush1g microarray signals were much lower in chick cochlea than those of Myo7a, Ush1c, Cdh23 and Pcdh15 and were not detected in the chick utricle. These experiments confirm the importance of MYO7A for the development and maintenance of bundle function and support the suggestion that MYO7A, USH1G (Sans) and CDH23 form the upper tip-link complex in adult mice, likely in combination with USH1C (harmonin). MYO7A, USH1G and PCDH15 may form another complex in stereocilia. USH1G may be a limiting factor in both complexes.
Hum Mol Genet 2012 Jun 01
PMID:Digenic inheritance of deafness caused by 8J allele of myosin-VIIA and mutations in other Usher I genes. 2238 27