Frequency of gjb2 and gjb6 gene mutations in arnshl patients of northwest iran

Aziz Khorrami,1 Saba dayem omid,2 Shahin behrouz sharif ,3 Mahan narjabadifam,4 Seyyed vahid mohaddes ardebili,5 Seyyed mojtaba mohaddes ardebili,6,*

1. Department of Genetics, Faculty of Natural Sciences, University of Tabriz
2. Drug Applied Research Center, Tabriz University of Medical Sciences
3. Department of Human Genetics, Faculty of Medicine, Tabriz University of Medical Sciences
4. Department of Genetics, Faculty of Natural Sciences, University of Tabriz
5. Department of Genetics, Faculty of Natural Sciences, University of Tabriz
6. Department of Human Genetics, Faculty of Medicine, Tabriz University of Medical Sciences

Abstract

Introduction

Autosomal recessive non-syndromic hearing loss (arnshl), as the most common form of hereditary hearing loss, has been reported to be associated with about 60 different loci and almost 30 different genes. mutations of gjb2 and gjb6, as most frequent mutated genes, contribute to alterations in dfnb1/a3 locus at 13q12. gjb2 mutations are comprised of point mutations, however, so far reported two large deletions are responsible for gjb6 mutations. this study was conducted to investigate mutation spectrum of these genes (in both coding regions and splice sites) among 150 arnshl patients from northwest of iran.

Methods

After being diagnosed as arnshl patients, total genomic dna of 150 individuals were studied using gap-pcr and direct sanger sequencing methods for gjb6 and gjb2 mutations analysis, respectively.

Results

Of studied subjects, 49/150 (32.6%) individuals demonstrated overall 10 distinct gjb2 mutations (c.35delg, ivs1+1g>a, c.84t>c, v37i, 167delt, 312del14, v153i, g127v, r127h, and v27i) that contributed to 28/150 (18.6%) homozygous and 21/150 (14%) compound heterozygous genotypes. c.35delg was the most frequent gjb2 mutation (18%) followed by ivs1+1g>a. gjb6 large deletions (d13s1830 and d13s1854) have not been detected among studies subjects.

Conclusion

Our results indicate the significance of gjb2 gene as a first priority for molecular study in arnshl patients of our population that can be of great importance in early diagnosis and genetic counseling; however, gjb6 seems to have very low mutation frequency and hence stands in later priorities.

Keywords

Arnshl, gjb2, gjb6, gap-pcr