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 "p" symptom

22q11.2 deletion syndrome

alexander disease

cadasil

cohen syndrome

familial hypocalciuric hypercalcemia

gm1 gangliosidosis

harlequin ichthyosis

lamellar ichthyosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

pendred syndrome

primary hyperoxaluria type 1

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