Report of Iranian Family with Pendred Syndrome with New Mutation T420I, and Multiply Heterozygous New Mutation T420I and 1197delT

The incidence of profound congenital hearing loss is about 1 in 1,000 live birth. There are more than 50 distinct genetic loci (known as DFNB loci) at which mutations can cause recessive hearing loss. DFNB4, one recessive locus for deafness, also maps to 7q31 considerably for nonsyndromic hearing loss and Pendred Syndrome which has been named PDS gene. Pendred syndrome (PS, MIM 274600) with an estimated frequency 1-8 per 100,000, is an autosomal recessive disorder and classically characterized by sensor neural hearing loss and goiter. Here, we reported a family with Pendred syndrome that in which a new mutation, T420I, in the homozygous state caused the condition. Also there was a 9-year-old boy in the related family with hearing loss and with no signs of thyroid dysfunction or goiter, whom was compound heterozygous for PDS mutations including 1197delT and T420I. Both of these mutations result to PDS syndrome. However we are not sure if the 9-year old boy show the goiter appearance in near future, but the results could be used as the prognostic factor. Consequently we should follow up the patient. Besides all, characterization of mutations in PDS gene can guide us to early diagnosis of Pendred syndrome and consequently early treatment of the patients maybe show the clinical features of hypothyroidism in later onset

Linkage Analysis for 50 Iranian Families with Autosomal Recessive Non-Syndromic Hearing Loss for DFNB21 Locus

Objective: Congenital hearing loss occurs in 1 out of 1000 births and about 50% of all cases are estimated to be of genetic origin. About 70% of hereditary hearing loss is non-syndromic with autosomal recessive inheritance accounting for 80% of the genetic load. To assess the importance of other loci in the Iranian population, we screened 50 consanguineous families with ARNSHL for DFNB21, which was linked to ARNSHL in Middle East countries.  Materials & Methods: 50 consanguineous families with at least three affected children, previously excluded by mutational analysis from GJB2 and GJB6 genes, were included in this study. We used three polymorphic markers including D11S1998, D11S4464, and D11S1299 in this study. Results: Two families were linked to DFNB21 and two novel mutations have been detected so far. In two families a 266 Del T mutation and a large 9611bp deletion that starts from intron 9 and includes exon 10 in TECTA gene were detected. Conclusion: This study showed that mutations in DFNB21 locus are the most common cause of ARNSHL in Iranian population. It seems that DFNB21 may play an important role in genetic load of ARNSHL in Iran. This will be confirmed by screening more families for this locus in Iranian deaf population