Screening for Mitochondrial A1555G Mutation among Assortative Mating Hearing Impaired Families in South India: Some Vital Insights

Abstract

Unravelling the mechanism of non-syndromic hearing loss (NSHL) through genetic studies have till date been perplexed by several factors such as genetic heterogeneity, multiple phenotypes, consanguinity and marriages between hearing impaired persons. A1555G mutation in the MT-RNR1 gene has been identified to be one of the most common mitochondrial mutations in several populations and it has been associated with both NSHL as well as aminoglycoside induced ototoxicity. Objective: A detailed study was carried out to screen for the prevalence of mitochondrial A1555G mutation among assortatively mating hearing impaired families from South India. Subjects and Methods: Owing to the variable phenotypic expressivity of this mutation, all the available family members (hearing and hearing impaired) in 106 assortatively mating hearing impaired families, (60 DXD and 46 DXN mating type), comprising of 616 members in all (277 HI individuals and 339 normal hearing family members) were screened for the presence of A1555G mutation by PCR-RFLP method. Mitochondrial A1555G mutation in the 12SrRNA gene was screened by PCR-RFLP method and confirmed by direct sequencing of entire 12SrRNA gene using suitable primers. Additionally, all the individuals carrying the A1555G mutation, along with their family members were screened for GJB2 gene mutations by direct sequencing method. Results: On screening 616 members belonging to 106 assortatively mating families for A1555G mitochondrial DNA mutation, we found seven members in a family with variable phenotypes ranging from normal hearing to moderately severe hearing loss, having this mutation with clear matrilineal transmission. Conclusions: A1555G mutation in the 12SrRNA gene has been identified to be one of the most common mitochondrial mutations and it has been associated with both non-syndromic hearing loss as well as aminoglycoside induced ototoxicity. This is the first report from India on the prevalence of A1555G mutation in normal hearing individuals indicating the impending need to screen this common mitochondrial mutation on a large scale not only among the hearing impaired families but also in the normal hearing Indian population.