Usher syndrome: Hearing loss, retinal degeneration and associated abnormalities

Biochim Biophys Acta. 2015 Mar;1852(3):406-20. doi: 10.1016/j.bbadis.2014.11.020. Epub 2014 Dec 4.

Abstract

Usher syndrome (USH), clinically and genetically heterogeneous, is the leading genetic cause of combined hearing and vision loss. USH is classified into three types, based on the hearing and vestibular symptoms observed in patients. Sixteen loci have been reported to be involved in the occurrence of USH and atypical USH. Among them, twelve have been identified as causative genes and one as a modifier gene. Studies on the proteins encoded by these USH genes suggest that USH proteins interact among one another and function in multiprotein complexes in vivo. Although their exact functions remain enigmatic in the retina, USH proteins are required for the development, maintenance and function of hair bundles, which are the primary mechanosensitive structure of inner ear hair cells. Despite the unavailability of a cure, progress has been made to develop effective treatments for this disease. In this review, we focus on the most recent discoveries in the field with an emphasis on USH genes, protein complexes and functions in various tissues as well as progress toward therapeutic development for USH.

Keywords: Hair bundle link; Inner ear hair cell; Periciliary membrane complex; Retina photoreceptor; Therapy; USH multiprotein complex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Loci*
  • Hair Cells, Auditory, Inner* / metabolism
  • Hair Cells, Auditory, Inner* / ultrastructure
  • Humans
  • Multiprotein Complexes* / genetics
  • Multiprotein Complexes* / metabolism
  • Retina* / metabolism
  • Retina* / ultrastructure
  • Retinal Degeneration / genetics
  • Retinal Degeneration / metabolism
  • Retinal Degeneration / pathology
  • Usher Syndromes* / genetics
  • Usher Syndromes* / metabolism
  • Usher Syndromes* / pathology

Substances

  • Multiprotein Complexes