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-syndromic hearing loss

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.