title: Hearing loss associated with enlargement of the vestibular aqueduct: mechanistic insights from clinical phenotypes, genotypes, and mouse models.
abstract: Enlargement of the vestibular aqueduct (EVA) is one of the most common inner ear malformations associated with sensorineural hearing loss in children. The delayed onset and progressive nature of this phenotype offer a window of opportunity to prevent or retard progression of hearing loss. EVA is not the direct cause of hearing loss in these patients, but rather is a radiologic marker for some underlying pathogenetic defect. Mutations of the SLC26A4 gene are a common cause of EVA. Studies of an Slc26a4 knockout mouse demonstrate that acidification and enlargement of the scala media are early events in the pathogenesis of deafness. The enlargement is driven by fluid secretion in the vestibular labyrinth and a failure of fluid absorption in the embryonic endolymphatic sac. Elucidating the mechanism of hearing loss may offer clues to potential therapeutic strategies.
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, 5 Research Court, Rockville, Maryland 20850-3320, USA. griffita@nidcd.nih.gov
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
authors.forename: Philine
authors.initials: P
authors.lastname: Wangemann
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000172:deficiency / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D027321:Anion Transport Proteins; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters