The GJB2 gene encoding the gap-junction protein connexin 26, was revealed to cause distinct forms of hearing impairment, in particular autosomal recessive non syndromic hearing impairment. Mutations in GJB2 are the most common cause of moderate-to-profound congenital inherited hearing impairment in numerous populations [10].
In Iraq, there was no more details about this type of mutations except Jarada et al [15] who was studied other variant mutations in GJB2 gene of Iraqi people who were resident in Jordan kingdom. Therefore, we performed this case-control study to investigate the role of c.235delC, c.35delG and c.167delT mutations in the GJB2 and their interaction with other environmental factors to susceptibility of this condition.
In fact, the literature review was showed that the distribution of connexin 26 (GJB2) mutations widely differs among ethnicities, GJB2 c.35delG variant is found in 60% of Caucasians, Northern Europeans and Turkish suffering from hereditary hearing loss [16, 17].
The results were revealed that the c. 35delG was evident in 75 (78.9%) consisting of 35 (36.8%) homozygous and 40 (42.1%) heterozygous genotypes of mutant alleles, which was agreed with (70%) prevalence of the c.35delG mutation recorded in Cuba and (74%) in Spain for studying patients by Yenitse et al from Cuba and Spain [18]. As well as, The GJB2 c.35delG mutation was recorded in (60%) of North European and Turkish who suffer from hereditary deafness [16, 17]. It was arranged among the highest mutation in GJB2 when compared with its frequency in other Arabic populations rates, the GJB2 mutations account in Algeria 40%, in Lebanon 33.3%, in Palestine 23%, in Tunisia 17% and in Jordanian 16.9%. However, this mutation very rare in Asian patients and it is frequently encountered GJB2 mutation in Caucasians [19]. Accordingly, the high level of this mutation may be due to exposure to chemical materials used in the wars that occured in the last decades.
Another less frequent frameshift mutation, c.235delC was reported in this study. Which detected in 54(56.8%) from all ARNSHL patients including 21 (22.1%) homozygous and 33 (34.7%) heterozygous genotypes of mutant alleles. Our results consistent with other studies that found the GJB2 235delC genetic mutation was presented in 12.2–33% of individuals with hereditary deafness [9, 10, 20]. The c.235delC mutation was found as the most common mutation cause premature protein termination in patients suffering from hearing loss in East and Southeast Asia, while lower frequencies was recorded in Oceania and Europe [21–23]. It was also presented in Japanese, Korean, and Mongolian populations also mutation in GJB2 was a significantly contributed to the recessive inheritance NSHL in the Chinese population and also appeared in other ethnic groups [13, 24–27].
The third mutation c.167delT in GJB2 gene, which was not appeared in our study subjects, was mainly presented in Ashkenazi Jews (7, 10, 28) . Also, this mutation was detected in a Palestinians group from Bethlehem [2], which representing that the variant of GJB2 mutant allele frequency also may be marked in the groups of the similar population.
The variation between various studies in type of GJB2 mutations and terms of frequency associated with ARNSHL may be due to several causes that include: sample size (large sample size increase the probability for detecting rare mutations), selection criteria of the patients, accuracy of genotyping method that employed and consanguineous marriage rate.