A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran

Abstract

Hearing loss is the most common sensory disorder worldwide and affects 1 of every 500 newborns. In developed countries, at least 50% of cases are genetic, most often resulting in nonsyndromic deafness (70%), which is usually autosomal recessive (∼80%). Although the cause of hearing loss is heterogeneous, mutations in GJB2 gene at DFNB1 locus are the major cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) in many populations. Our previous study showed that mutations of GJB2 gene do not contribute to the major genetic load of deafness in the Iranian population (∼16%). Therefore, to define the importance of other genes in contributing to an ARNSHL phenotype in the Iranian population, we used homozygosity mapping to identify regions of autozygosity-by-descent in 144 families which two or more progeny had ARNSHL but were negative for GJB2 gene mutations. Using flanking or intragenic short-tandem repeat markers for 33 loci we identified 33 different homozygous variations in 10 genes, of which 9 are novel. In aggregate, these data explain ∼40% of genetic background of ARNHSL in the Iranian population.

The role and spectrum ofSLC26A4mutations in Iranian patients with autosomal recessive hereditary deafness

“…The frequency and spectrum of SLC26A4 mutations are different among various deaf populations ( 9.1% of total investigated alleles. The frequency of SLC26A4 mutations among the Iranian HL patients has been reported to be 10% and 4.8% in two previous studies (Kahrizi et al, 2009;Babanejad et al, 2012). Thus, the results of our research with a relatively higher sample size, confi rm the fi nding obtained by Kahrizi and colleagues (Kahrizi et al, 2009).…”

“…Thus, the results of our research with a relatively higher sample size, confi rm the fi nding obtained by Kahrizi and colleagues (Kahrizi et al, 2009). The discrepancy between results obtained with our investigation and that performed by Babanejd and colleagues (Babanejad et al, 2012) might be due to ethnicity differences. Notably, the result of the present study might be an overestimation since they include heterozygotes with a second unidentifi ed mutation .…”

“…Up to now, most studies about the genetics of deafness in Iran have been performed on GJB2 . Based on previous works (Kahrizi et al, 2009;Babanejad et al, 2012), we launched the current study in a cohort of Iranian HL families, with no GJB2 mutations, to investigate SLC26A4 mutations using molecular tools.…”

Investigation ofATP6V1B1andATP6V0A4genes causing hereditary hearing loss associated with distal renal tubular acidosis in Iranian families

“…4 In the Iranian population, where there is a high rate of consanguineous marriage, 5 autosomal recessive disorders such as hearing loss are some of the most common disabilities, affecting 1 in every 166 persons. 2 Syndromic hearing impairment associated with distal renal tubular acidosis is caused by a defect in acid-base homeostasis in kidney α-intercalated cells and inner-ear endolymphatic sacs. In the kidney, pH abnormalities lead to low serum potassium (K + ), elevated urinary calcium (Ca 2+ ), nephrocalcinosis (renal deposition of calcium salts), and a normal or nearnormal anion gap resulting from hyperchloraemic acidosis.…”

Consanguineous Marriage, Reproductive Behaviour and Postnatal Mortality in Contemporary Iran

“…primary immunodeficiencies resulting in increased susceptibility to infectious disease(s) [51,52] , or chronic childhood kidney disorders [53,54] . However, in terms of absolute numbers, recessive disorders that are common and not restricted to any single community, such as non-syndromic hearing impairment [55,56] and intellectual and developmental disabilities [57,58] , should show the most obvious future decline in prevalence.…”