title: Identification of a founder mutation for Pendred syndrome in families from northwest Iran.
abstract: OBJECTIVE
  Mutations in the SLC26A4 gene cause both Pendred syndrome and autosomal recessive nonsyndromic hearing loss (ARNSHL) at the DFNB4 locus. The SLC26A4 mutations vary among different communities. Previous studies have shown that mutations in the SLC26A4 gene are responsible for the more common syndromic hereditary hearing loss in Iran. This study assesses the possibility of a founder mutation for Pendred syndrome in northwest Iran.
  
  
  METHODS
  In this study, we performed comprehensive clinical and genetic evaluations in two unrelated families from northwest Iran with nine members affected by hearing loss (HL). After testing short tandem repeat (STR) markers to confirm linkage to the SLC26A4 locus, we screened the SLC26A4 gene by Sanger sequencing of all 21 exons, exon-intron boundaries and the promoter region for any causative mutation. We identified the same causative mutation in these two families as we had detected earlier in two other Azeri families from northwest Iran. To investigate the possibility of a founder effect in these four families, we conducted haplotype analysis, and 14 single nucleotide polymorphisms (SNPs) throughout the SLC26A4 gene were genotyped.
  
  
  RESULTS
  Patients in the two families showed the phenotype of Pendred syndrome. A known frameshift mutation (c.965insA, p.N322Fs7X) in exon 8 was identified in the two families, which was the same mutation that we detected previously in two other Azeri families. The results of haplotype analysis showed that all 15 patients from four families shared the founder mutation. Common haplotypes were not observed in noncarrier members.
  
  
  CONCLUSIONS
  Based on the results of our two studies, the c.965insA mutation has only been described in Iranian families from northwest Iran, so there is evidence for a founder mutation originating in this part of Iran.
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Mohseni
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran.
authors.forename: Asal
authors.initials: A
authors.lastname: Honarpour
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Mozafari
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran.
authors.forename: Behzad
authors.initials: B
authors.lastname: Davarnia
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences (USWR), Tehran, Iran. Electronic address: kahrizi@yahoo.com.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005091:Exons; D005260:Female; D018703:Founder Effect; D016368:Frameshift Mutation; D005838:Genotype; D006044:Goiter, Nodular / Q000235:genetics*; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007492:Iran; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D020641:Polymorphism, Single Nucleotide; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: Founder mutation; Haplotype analysis; Iran; Linkage analysis; Pendred syndrome; SLC26A4 gene