title: A novel mutation in the pendrin gene associated with Pendred's syndrome.
abstract: OBJECTIVE
  Pendred's syndrome is an autosomal recessive disorder characterized by goitre, sensorineural deafness and iodide organification defect. It is one of the most frequent causes of congenital deafness, accounting for about 10% of hereditary hearing loss. It is caused by mutations in the pendrin (PDS) gene, a 21 exon gene located on chromosome 7. The aim of this study was to examine an Italian family affected with Pendred's syndrome at the molecular level.
  
  
  METHODS
  Thirteen subjects belonging to a family from Southern Italy were evaluated for the clinical and genetic features of Pendred's syndrome.
  
  
  METHODS
  Exons 2-21 of the PDS gene were amplified from peripheral leucocytes by the polymerase chain reaction; mutation analysis was performed by single strand conformation polymorphism, direct sequencing and restriction analysis.
  
  
  RESULTS
  The index patient had the classical triad of the syndrome and harboured two mutations in the PDS gene in the form of compound heterozygosity. He was found to be heterozygous for a cytosine to adenosine mutation at nucleotide 1523 in exon 13 and for a IVS 1001 + 1G --> A mutation. The former is a novel mutation which results in a change of 508 threonine to asparagine in the putative eleventh transmembrane domain. The latter mutation in the donor splice site has already been described in other patients and is thought to lead to aberrant splicing and premature protein truncation. Three subjects who were heterozygous for one mutation had normal phenotypes. Two subjects had sensorineural deafness and were heterozygous for a single mutation. Goitre was found only in patients with Pendred's syndrome and was absent in all other individuals, albeit residing in an iodine-deficient area.
  
  
  CONCLUSIONS
  We have identified a novel mutation in the pendrin gene causing Pendred's syndrome, and confirm that molecular analysis is a useful tool for a definitive diagnosis. This is particularly relevant in cases such as in the subjects of our family in which the clinical features might be misleading and other genetics factors might be responsible for deafness.
authors.affiliation: Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, University of Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Bogazzi
authors.forename: F
authors.initials: F
authors.lastname: Raggi
authors.forename: F
authors.initials: F
authors.lastname: Ultimieri
authors.forename: A
authors.initials: A
authors.lastname: Campomori
authors.forename: C
authors.initials: C
authors.lastname: Cosci
authors.forename: S
authors.initials: S
authors.lastname: Berrettini
authors.forename: E
authors.initials: E
authors.lastname: Neri
authors.forename: R
authors.initials: R
authors.lastname: La Rocca
authors.forename: G
authors.initials: G
authors.lastname: Ronca
authors.forename: E
authors.initials: E
authors.lastname: Martino
authors.forename: L
authors.initials: L
authors.lastname: Bartalena
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D007758:Ear, Inner / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006042:Goiter / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007454:Iodides / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins; D010375:Pedigree; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D015183:Restriction Mapping; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters; D013577:Syndrome; D014057:Tomography, X-Ray Computed
chemical_list: D002352:Carrier Proteins; D007454:Iodides; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters