title: Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4 mutations in Pendred syndrome/enlarged vestibular aqueducts.
abstract: BACKGROUND
  Pendred syndrome is a common autosomal recessive disorder causing deafness. Features include sensorineural hearing impairment, goitre, enlarged vestibular aqueducts (EVA) and occasionally Mondini dysplasia. Hearing impairment and EVA may occur in the absence of goitre or thyroid dyshormonogensis in a condition known as non-syndromic EVA. A significant number of patients with Pendred syndrome and non-syndromic EVA show only one mutation in SLC26A4. Two genes, KCNJ10, encoding an inwardly rectifying potassium channel and FOXI1, a transcriptional factor gene, are thought to play a role in the disease phenotypes.
  
  
  METHODS
  Using Polymerase Chain Reaction and Sanger sequencing, sixty-eight patients with monoallelic mutations of SLC26A4 were tested for mutations in KCNJ10 and FOXI1.
  
  
  RESULTS
  Two variants were observed in the KCNJ10 gene, p.Arg271Cys in three patients and p.Arg18Gln in one patient; only one variant, p.Arg123Trp was observed in the FOXI1 gene in a single patient. Both p.Arg271Cys and p.Arg18Gln are likely to be polymorphisms as judged by their frequency in the general population.
  
  
  CONCLUSIONS
  Therefore we found no evidence for a significant association between mutations of KCNJ10 and FOXI1 with SLC26A4. It was also observed that the variant, p.Arg271Cys in KCNJ10, previously thought to have a protective effect against seizure susceptibility, was found in a patient with Pendred syndrome with co-existing epilepsy.
authors: North East Thames Regional Genetics Service Laboratory, Great Ormond Street Hospital for Children NHS Foundation Trust, 37 Queen Square,York House, London WC1N 3BH, UK.
authors: Priya
authors: P
authors: Landa
authors: Ann-Marie
authors: AM
authors: Differ
authors: Kaukab
authors: K
authors: Rajput
authors: Lucy
authors: L
authors: Jenkins
authors: Maria
authors: M
authors: Bitner-Glindzicz
mesh_terms: D000483:Alleles; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006042:Goiter / Q000235:genetics; D006044:Goiter, Nodular / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters; 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
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