[Frequency of the common mitochondrial DNA [mtDNA] mutations in non-syndromic hearing impairment in southwest subpopulations of Iran]

Although, most hereditary non-syndromic hearing impairment [NSHI] is due to mutation in nuclear genes, role of mtDNA mutations in causing deafness becoming much more clear in recent years. The aim of the present study was to screen the A1555G, C1494T, A3243G and A7445G mutations in non-syndromic hearing impairment patients in two provinces of southwest of Iran. In this descriptive laboratory study, 150 subjects with acquired and prelingual autosomal recessive NSHI from Chaharmahal va Bakhtiari province and 46 unrelated probands with postlingual NSHI from Bushehr province [negative for GJB2 mutations] were screened for the presence of the common mtDNA mutations using PCR-RFLP method that followed by direct sequencing for confirming the observed mtDNA mutations. None of these mutations was found in subjects with acquired and prelingual autosomal recessive NSHI from Chaharmahal va Bakhtiari province, but mutation A1555G with frequency of 4.35% was found in postlingual NSHI patients in Bushehr province. This investigation shows that apparently, mtDNA mutations play a more significant role role in the etiology of postlingual NSHI in comparison with prelingual NSHI

Genetic linkage analysis of 15 DFNB loci in a group of Iranian families with autosomal recessive hearing loss

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. 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. Sixteen families were found to be linked to seven different known loci, including DFNB1 [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. 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

[Mutation screening of GJB2 and GJB6 and genetic linkage study of three prevalent DFNB loci in Iranian families with autosomal recessive non-syndromic hearing loss]

The incidence of prelingual hearing loss [HL] is about 1 in 1000 neonates of which, more than 60% of cases are inherited. Non-syndromic HL [NSHL] is extremely heterogeneous: more than 100 loci have been identified. The most common form of NSHL is the autosomal recessive form [ARNSHL]. Here, we have investigated CX26 [GJB2] and CX30 [GJB6] gene mutation and linkage analysis of 3 known loci in Iranian families. A cohort of 36 big ARNSHL pedigrees from 7 provinces of Iran was investigated. All of the families were examined for the presence of GJB2 and GJB6 [del D13S1830 and del D13S1854] mutations using direct sequencing and multiplex PCR, respectively. The negative mutations pedigrees for the above-mentioned mutations, were then tested for the linkage to the 3 known loci, including DFNB3[MYO7A], DFNB4[SLC26A4] and DFNB7/11[TMC1], using STR markers and conventional PCR and PAGE. Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4 and 1 family was linked to DFNB7/11. DFNB1 [GJB2] and DFNB4 are the main causes of ARNSHL in our study samples and GJB6 mutations are apparently absent in the Iranian population

Frequencies of mutations in the connexin 26 gene [GJB2] in two populations of Iran [Tehran and Tabriz]

While hearing loss has been considered to be a very heterogeneous disorder, mutations in Gap junction beta 2 [GJB2] gene encoding Connexin 26 [Cx26] protein are the major cause of autosomal recessive and sporadic non-syndromic deafness in many populations. In this study, we have investigated the prevalence of the GJB2 gene mutations using nested PCR pre screening strategy and direct sequencing method. Two hundred and seventy two hearing impaired subjects were studied from 210 families obtained from two large cities of Iran [Tehran and Tabriz]. Twenty four different genetic variants were identified. Cx26 mutations were found in 53 of the 210 families [25.2%] including T8M, 35delG, W24X, R32H, V37I, E47X, 167delT, delE120, Y136X, R143W, R184P, 235delC and V27I+E114G. Homozygosity and compound heterozygosity for the Cx26 mutations were found in 39 of 210 [18.5%] families. Homozygosity for the 35delG mutation was the most common that causes hearing loss in 28 [13.3%] patients. Six novel variants H16R, E101E, K102Q, G200R, 327delG and G130A were detected in this study. As a conclusion, the present survey revealed that the rate of mutation in Cx26 gene in our area is lower than in Europe; nevertheless, this rate is regarded as a considerable cause of deafness in the cited provinces in Iran

Report of a new mutation and frequency of connexin 26 gene [GJB2] mutations in patients from three provinces of Iran

Autosomal recessive and sporadic non-syndromic hearing loss [ARSNSHL] is the major form of hereditary deafness.Mutations in the GJB2 gene encoding the gap-junction protein Connexin 26 have been identified to be highly associated with ARSNSHL. In this study we have analyzed 196 deaf subjects from 179 families having one or more deaf children in 3 proviences of Iran, including Kordestan, Khuzestan and Golestan. The nested PCR prescreening strategy and direct sequencing technique were used to detect the mutations in coding exon of the gene. Altogether 3 GJB2 recessive mutations including 35delG, 167delT and V27I+E114G, were identified in 23 of 179 families [12.8%]. Fourteen of 179 families were observed to have GJB2 mutation in both alleles [7.8%]. A novel variant [R159H] also was found in a deaf family from Khuzestan. Four polymorphisms V27I, E114G, S86T and V153 I also were detected in 7 families. A polymorphism [S86T] was seen in the whole population studied. Our data indicated that the rate of connexin 26 mutations is different in this three Irainian population and is lower than the high frequency of 35delG [26%] reported from Gilan province in the north of Iran

Frequency of a very rare 35delG mutation in two ethnic groups of iranian population

The 35delG mutation in the Connexin 26 gene [Cx26], at the DNFB1 locus is the most common mutation in the patients with autosomal recessive non-syndromic hearing loss [ARNSHL]. We have studied a total of 224 deaf cases from 189 families in two populations of Iran [Sistan va Bluchestan and Hormozgan provinces] by prescreening nested PCR, polyacrylamide gel electrophoresis and consequent direct sequencing method for all cases. The aim of the present work was to find prevalence of GJB2 mutations in the populations studied. Four different GJB2 mutations including 35delG, W24X, R127H and [V27I + E114 G] were identified in 11 of 189 families [5.8%]. Two polymorphisms [V27I and V153I] also were detected in 14 families. A polymorphism S86T was determined in all cases. Homozygote 35delG mutation was found only in 1 of 189 families [0.5%].The rate of Cx26 mutations found in this study was lower than other Iranian populations. So the cause of deafness in the populations studied remains to be detected in other loci or genes