title: Identification of SLC26A4 mutations in patients with hearing loss and enlarged vestibular aqueduct using high-resolution melting curve analysis.
abstract: Mutations in the SLC26A4 gene can cause both Pendred syndrome and nonsyndromic enlargement of the vestibular aqueduct, two conditions associated with sensorineural hearing loss. We analyzed the SLC26A4 gene in 44 hearing-impaired patients by nested polymerase chain reaction followed by high-resolution melt analysis. We also used this approach to scan for mutations in KCNJ10 and FOXI1, two genes reported to play a role in the pathogenesis of Pendred syndrome and enlarged vestibular aqueduct. Seven patients with known SLC26A4 mutations were included as controls. All previously identified mutations were detected by high-resolution melt analysis. Of the patients with no known mutations, we detected two SLC26A4 mutations in 5 probands (12%), one mutation in 9 probands (21%), and no mutations in 29 probands (67%). We identified two novel SLC26A4 mutations, p.T485M and p.F718S, and found no evidence of a digenic contribution of KCNJ10 and FOXI1 mutations.
authors.affiliation: Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville, Melbourne, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Mercer
authors.forename: Patricia
authors.initials: P
authors.lastname: Mutton
authors.forename: Hans-Henrik M
authors.initials: HH
authors.lastname: Dahl
mesh_terms: D002779:Cholestasis; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006044:Goiter, Nodular / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D011014:Pneumonia; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters; D044366:Transition Temperature; D014723:Vestibular Aqueduct / Q000473:pathology*; D000098854:Kcnj10 Channel
chemical_list: C477894:FOXI1 protein, human; D051858:Forkhead Transcription Factors; D000098854:Kcnj10 Channel; D026901:Membrane Transport Proteins; D024661:Potassium Channels, Inwardly Rectifying; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters