Identification of a founder mutation for Pendred syndrome in families from northwest Iran.

[pendred syndrome]

Mutations in the SLC 26 A 4 gene cause both Pendred syndrome and autosomal recessive nonsyndromic hearing loss (ARNSHL ) at the DFNB 4 locus . The SLC 26 A 4 mutations vary among different communities . Previous studies have shown that mutations in the SLC 26 A 4 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 .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 SLC 26 A 4 locus , we screened the SLC 26 A 4 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 SLC 26 A 4 gene were genotyped .Patients in the two families showed the phenotype of Pendred syndrome . A known frameshift mutation (c .965 insA , p .N 322 Fs 7 X ) 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 .Based on the results of our two studies , the c .965 insA 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 .

Diseases
Validation

Diseases presenting "hearing loss" symptom

22q11.2 deletion syndrome

achondroplasia

adrenomyeloneuropathy

alexander disease

benign recurrent intrahepatic cholestasis

canavan disease

cohen syndrome

congenital toxoplasmosis

dentinogenesis imperfecta

fabry disease

familial mediterranean fever

heparin-induced thrombocytopenia

hirschsprung disease

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

neonatal adrenoleukodystrophy

pendred syndrome

von hippel-lindau disease

wolf-hirschhorn syndrome

This symptom has already been validated