title: Molecular analysis of SLC26A4 gene in patients with nonsyndromic hearing loss and EVA: identification of two novel mutations in Brazilian patients.
abstract: The SLC26A4 gene has been described as the second gene involved in most cases of sensorineural non-syndromic hearing loss, since the first is the GJB2 gene. Recessive mutations in the SLC26A4 gene encoding pendrin, an anion transporter, are responsible for non-syndromic hearing loss associated with an enlarged vestibular aqueduct (EVA) and Pendred syndrome, which causes early hearing loss and affects the thyroid gland. Typically, the hearing loss is profound and prelingual. However, in some individuals, hearing impairment may develop later in childhood and then progress. Over 200 different SLC26A4 mutations have been reported, with each ethnic population having its own distinctive mutant allele series including a few prevalent founder mutations.
  
  
  OBJECTIVE
  Perform the screening of the 20 coding exons of SLC26A4 gene in Brazilian deaf individuals with EVA.
  
  
  METHODS
  Among the 23 unrelated non-syndromic hearing loss Brazilian patients with EVA, in whom no deafness-causing mutations of the GJB2 gene, the direct sequencing was performed to screen the 20 exons and their flanking regions of the SLC26A4 gene.
  
  
  RESULTS
  The sequencing results revealed 9 cases (39%) carrying 13 different SLC26A4 mutations, including 11 known mutations (279delT, V138F, T193I, IVS8+1G>A, T410M, Q413R, R409H, L445W, IVS15+5G>A, V609G, and R776C) and 2 novel mutation (G149R and P142L).
  
  
  CONCLUSIONS
  The SLC26A4 mutations have a high carrying rate in non-syndromic hearing loss Brazilian patients. The identification of a disease-causing mutation can be used to establish a genotypic diagnosis and provide important information to the patients and their families.
authors.affiliation: Center of Molecular Biology and Genetic Engineering (CBMEG), Molecular Biology Laboratory, State University of Campinas - UNICAMP, Campinas, São Paulo, Brazil. moraes.van@gmail.com
authors.forename: Vanessa Cristine Sousa
authors.initials: VC
authors.lastname: de Moraes
authors.forename: Nathalia Zocal Pereira
authors.initials: NZ
authors.lastname: dos Santos
authors.forename: Priscila Zonzini
authors.initials: PZ
authors.lastname: Ramos
authors.forename: Maria Carolina Costa Melo
authors.initials: MC
authors.lastname: Svidnicki
authors.forename: Arthur Menino
authors.initials: AM
authors.lastname: Castilho
authors.forename: Edi Lúcia
authors.initials: EL
authors.lastname: Sartorato
mesh_terms: D000293:Adolescent; D000328:Adult; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D008403:Mass Screening; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26