Genetic Linkage Analysis of 15 DFNB Loci in a Group of Iranian Families with Autosomal Recessive Hearing Loss

Background: Hearing loss (HL) is the most frequent sensory birth defect in humans. Autosomal recessive non-syndromic HL (ARNSHL) is the most common type of hereditary HL. It is extremely heterogeneous and over 70 loci (known as DFNB) have been identified. This study was launched to determine the relative contribution of more frequent loci in a cohort of ARNSHL families. Methods: Thirty-seven Iranian families including 36 ARNSHL families and 1 family with Pendred syndrome each with >= 4 affected individuals, from seven provinces of Iran, were ascertained. DFNB1 contribution was initially studied by DNA sequencing of GJB2 and linkage analysis using the relative STR markers. The excluded families were then subjected to homozygosity mapping for fifteen ARNSHL loci. Results: Sixteen families were found to be linked to seven different known loci, including DFNB I (6 families), DFNB4 (3 families +1 family with Pendred syndrome), DFNB63 (2 families), DFNB2 (1 family), DFNB7/11 (1 family), DFNB9 (1 family) and DFNB21 (1 family). DNA sequencing of the corresponding genes is in progress to identify the pathogenic mutations. Conclusion: The genetic causes were clarified in 43.2% of the studied families, giving an overview of the causes of ARNSHL in Iran. DFNB4 is ranked second after DFNB1 in the studied cohort. More genetic and epigenetic investigations will have to be done to reveal the causes in the remaining families

Screening of three common mtDNA mutations among subjects with autosomal recessive non-syndromic hearing loss in Sistan va Baluchestan province, Iran

Background: Non-syndromic hearing loss may be induced by mutations in both nuclear and mitochondrial genes. Mutations in mtDNA are present in less than 1% of the children with pre-lingual deafness but are more prevalent later. Most of the molecular defects responsible for mitochondrial disorder, associated with hearing loss may be induced by mutations in the 12SrRNA and tRNA genes. This aim of this study was to investigate the frequency of three common mtDNA mutations including A1555G, A3243G and A7445G in a cohort of autosomal recessive non-syndromic hearing loss (ARNSHL) subjects in Sistan va Baluchestan province. Material and Methods: In this descriptive- experimental based study, a total of 110. ARNSHL subjects from Sistan va Baluchestan province were investigated for three common mtDNA mutations using PCR-RFLP procedure. The possible mutations were confirmed by direct sequencing. Results: None of the A1555G and A7445G mutations were detected in this study. However, we found one sample to carry A3243G mutation (0.9%). Moreover abolishing a MTTL1 restriction site close to A3243G mutation revealed a G3316A allelic variant in 0.9% of patients studied. Conclusion: This study showed that mtDNA mutations are responsible for less than 1% of pre-lingual ARNSHL associated subjects. The present study will improve the genetic counseling of hearing impaired patients in Sistan va Baluchestan province, Iran

DFNB59 Gene Mutation Screening Using PCR-SSCP/HA Technique in Non-syndromic Genetic Hearing Loss in Bushehr Province

Background: Hearing impairment (HI) is the most prevalent Neurosensory disorder which is heterogenous and can also occur due to environmental causes. The majority of hearing deficiencies are of genetic origin affecting about 60% of the HI cases. A novel gene DFNB59 encodes pejvakin has been recently shown to cause deafness. This study aims to determine the frequency of DFNB59 gene mutations in coding region the gene in Bushehr province. Methods: In this descriptive experimental study, we investigated the presence of DFNB59

Large-Scale Screening of Mitochondrial DNA Mutations Among Iranian Patients with Prelingual Nonsyndromic Hearing Impairment

Hereditary hearing impairment (HI) is a genetically heterogeneous disorder caused by mutations either in nuclear DNA (nDNA) or in mitochondrial DNA (mtDNA). The nDNA mutations account for the majority of prelingual nonsyndromic HI (NSHI). The present survey was conducted to screen for known pathogenic mtDNA mutations including A1555G, A3243G, C1494T, and A7445G to provide an accurate estimate of their prevalence in prelingual NSHI for the first time in the Iranian subpopulations. One thousand unrelated probands with NSHI (including both GJB2-negative and GJB2 heterozygote cases) and 1000 healthy matched controls were investigated using the PCR/RFLP method followed by DNA sequencing to confirm the observed mtDNA mutations. Two of the studied mutations, namely A3243G and A7445G, were each found in a single family (a frequency of 0.1% for each). Mutation screening for A3243G followed by DNA sequencing led to the identification of G3316A substitution, with no prior link to HI. Surprisingly, screening for A3243G in the studied population identified 6 cases (0.6%) in probands and 10 (1%) in normal subjects. A1555G, the most common mtDNA mutation associated with deafness in other populations, was not found in the studied samples. To conclude, our findings indicate G3316A as a nonpathogenic variant in the prelingual NSHI subpopulations of Iran and suggest that mtDNA mutations do not play a major role in the etiology of NSHI in Iran

DFNB59 Gene Mutation Screening Using PCR-SSCP/HA Technique in Non-syndromic Genetic Hearing Loss in Bushehr Province

Background: Hearing impairment (HI) is the most prevalent Neurosensory disorder which is heterogenous and can also occur due to environmental causes. The majority of hearing deficiencies are of genetic origin affecting about 60% of the HI cases. A novel gene DFNB59 encodes pejvakin has been recently shown to cause deafness. This study aims to determine the frequency of DFNB59 gene mutations in coding region the gene in Bushehr province. Methods: In this descriptive experimental study, we investigated the presence of DFNB59 gene mutations in Exons (2-7) of the gene in 80 deaf subjects. DNA was extracted using standard phenol –chloroform method. The screening of gene mutations was performed by PCR-SSCP/HA procedure. Finally, the possible mutations were confirmed by direct sequencing. Results: In all, 9 polymorphisms 793C>G were found in 80 non-syndromic, genetic hearing loss subjects studied. However no DFNB59 gene mutation was identified. Conclusion: We conclude that the association of DFNB59 gene mutations with hearing loss is very low in samples studie