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 populations

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. © 2014, Iranian Journal of Public Health. All rights reserved

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

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

Background and aim: 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. Methods: 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. Results: 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. Conclusion: DFNB1 (GJB2) and DFNB4 are the main causes of ARNSHL in our study samples and GJB6 mutations are apparently absent in the Iranian populatio

Mutation analysis of GJB2 and GJB6 genes and the genetic linkage analysis of five common DFNB loci in the Iranian families with autosomal recessive non-syndrom

The incidence of pre-lingual hearing loss (HL) is about 1 in 1000 neonates. More than 60% of cases are inherited. Non-syndromic HL (NSHL) is extremely heterogeneous: more than 130 loci have been identified so far. The most common form of NSHL is the autosomal recessive form (ARNSHL). In this study, a cohort of 36 big ARNSHL pedigrees with 4 or more patients 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 methods, respectively. The negative pedigrees for the above-named genes were then tested for the linkage to 5 known loci including DFNB3 (MYO7A), DFNB4 (SLC26A4), DFNB7/11 (TMC1), DFNB21 (TECTA) and DFNB59 (PJVK) by genotyping the corresponding STR markers using PCR and PAGE. Six families had GJB2 mutations. No GJB6 mutation was found. Totally, 3 families showed linkage to DFNB4, 1 family to DFNB7/11 and 1 family to DFNB21. No family was linked to DFNB59. GJB2 included 16.6% of the causes of ARNSHL in our study. In the remaining negative families, DFNB4 accounted for 10% of the causes. Other loci including DFNB7/11 and DFNB21 were each responsible for 3.3% of the etiology. Thus, DFNB1(GJB2) and DFNB4 are the main causes of ARNSHL in our study and GJB6 mutations (del D13S1830, del D13S1854), DFNB3 and DFNB59 were absent. Totally, 30.5% of the ARNSHL etiology was found in this study

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, V371, 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

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

Autosomal recessive and sporadic non syndromic hearing loss and the incidence of Cx26 mutations in a province of Iran

Despite the enormous heterogeneity of genetic hearing loss, mutations in the GJB2 (connexin 26) gene located on "DFNB1" locus (13q12) account for up to 50 of cases of autosomal recessive non-syndromic hearing loss (ARNSHL) in some populations. This study describes the analysis of 100 autosomal recessive and sporadic nonsyndromic hearing loss individuals from 79 families each having at least one deaf child in Chehar Mahal va Bakhtiari province in west of Iran. We have investigated the prevalence of the connexin 26 gene mutations using nested PCR strategy to screen the predominant 35delG mutation and subsequent direct sequencing to detect other Cx26 mutations. Seven different genetic variants were detected from which one novel variant was including 363delC. The 35delG was the most common mutation found in 5 of 79 families (6.3). Cx26 related deafness mutations (35delG,V27I; E114G) and R127H) were found in 12 of 158 chromosomes studied (7.8%). We conclude that the association of Cx26 mutations with deafness in Chehar Mahal va Bakhtiari province is low and looks like most other populations of 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

Frequency of the mitochondrial A1555G mutation in Iranian patients with non-syndromic hearing impairment

Mitochondrial 12S rRNA gene mutations account for non-syndromic hearing impairment (NSHI). The A1555G substitution is the most common mitochondrial DNA mutation and is associated with both aminoglycoside-induced HI and NSHI. Its frequency is variable among populations of different ethnic background. The purpose of the present survey was to determine the frequency of the A1555G mutation in the Iranian probands with NSHI. We have screened 152 unrelated Iranian probands with NSHI with childhood onset and 548 normal hearing controls for the occurrence of the A1555G mutation using PCR-RFLP method. Totally, 2 patients carrying the homoplasmic A1555G mutation were identified with a total frequency of 1.3 in Iran. Mutation A1555G had a variable frequency among subpopulations of different ethnic origins in Iran: Azeri Turkish (4.16), Lure (0.0), Fars (0.0) and Bushehri (2.86). The A1555G mutation was not found in any member of the controls. Our study shows that the frequency of the A1555G mutation in Azeri Turkish and Bushehri hearing impaired patients is compatible with that reported for Caucasian populations