Compound Heterozygosity for Two Novel Mutations in a Large Iranian Pedigree with Pendred Syndrome

Abstract

ObjectivesThe aim of this study was to detect the genetic cause of deafness in a large Iranian family. Due to the importance of SLC26A4 in causing hearing loss, information about the gene mutations can be beneficial in molecular detection and management of deaf patients.MethodsWe investigated the genetic etiology in a large consanguineous family with 9 deaf patients from Fars province of Iran with no GJB2 mutations. Initially, linkage analysis was performed by four DFNB4 short tandem repeat markers. The result showed linkage to DFNB4 locus. Following that, DNA sequencing of all 21 exons, their adjacent intronic sequences and the promoter of SLC26A4 was carried out for mutation detection.ResultsTwo novel mutations (c.863-864insT and c.881-882delAC) were identified in exon 7 of the gene, in both homozygous and compound heterozygous state in patients.ConclusionOur results supported the importance of the SLC26A4 mutations in the etiology of hearing loss among the Iranian patients and therefore its mutation screening should be considered after GJB2 in the molecular diagnostics of hearing loss, especially when enlarged vestibular aqueduct or goiter is detected.

Keywords

• Novel mutation
• Compound heterozygosity
• SLC26A4
• Pendred syndrome
• Hearing loss
• Linkage analysis
• Iran