title: A novel SLC26A4 (PDS) deafness mutation retained in the endoplasmic reticulum.
abstract: OBJECTIVE
  To identify mutations in the SLC26A4 gene in individuals with nonsyndromic hearing loss and enlarged vestibular aqueduct, to design a predicted model of the pendrin protein, and to characterize novel mutations by means of localization in mammalian cells and effect of the mutation on the predicted model.
  
  
  METHODS
  Validation of the mutation by its exclusion in more than 300 individuals with normal hearing.
  
  
  METHODS
  A laboratory of genetics of hearing loss research, clinical genetics laboratories, an otolaryngology department at Tel Aviv University, and medical centers in Israel.
  
  
  METHODS
  A patient with nonsyndromic hearing loss and enlarged vestibular aqueduct, 203 deaf probands, and 310 controls with normal hearing.
  
  
  METHODS
  Sequencing the SLC26A4 gene in the patient with nonsyndromic hearing loss and enlarged vestibular aqueduct. Transfection of yellow fluorescent protein (YFP) constructs into mammalian COS7 cells. Designing a computational model of the human SLC26A4 protein.
  
  
  METHODS
  Detection of a novel c.1458_1459insT SLC26A4 mutation.
  
  
  RESULTS
  A computational model of the human pendrin protein suggests that the novel c.1458_1459insT mutation leads to a prematurely truncated protein, p.Ile487TyrfsX39. Mammalian COS7 cells transfected with the YFP-1458_1459insT construct showed mislocalization of the mutant protein.
  
  
  CONCLUSIONS
  A novel SLC26A4 mutation was detected in Israel. Because current estimates demonstrate that SLC26A4 mutations are involved in up to 4% of nonsyndromic deafness, our findings emphasize the importance of adding a molecular test for the SLC26A4 gene in the diagnosis of deafness, particularly when bone abnormalities are involved, to the list of genes screened in Israel and elsewhere in the world.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. brownste@post.tau.ac.il
authors.forename: Zippora N
authors.initials: ZN
authors.lastname: Brownstein
authors.forename: Amiel A
authors.initials: AA
authors.lastname: Dror
authors.forename: Dror
authors.initials: D
authors.lastname: Gilony
authors.forename: Lela
authors.initials: L
authors.lastname: Migirov
authors.forename: Koret
authors.initials: K
authors.lastname: Hirschberg
authors.forename: Karen B
authors.initials: KB
authors.lastname: Avraham
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002648:Child; D003638:Deafness / Q000208:ethnology / Q000235:genetics*; D004721:Endoplasmic Reticulum / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D007557:Israel; D007585:Jews / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities*
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters