Is Screening for Mitochondrial A1555G Mutation among Assortative Mating Hearing Impaired Families Important? : A Prefatory Quest

Genetic heterogeneity, multiple phenotypes, consanguinity and marriages between hearing impaired persons have confounded the genetic studies on non-syndromic hearing loss (NSHL). 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 NSHL as well as aminoglycoside induced ototoxicity. Objective: To screen for the prevalence of mitochondrial A1555G mutation among assortatively mating hearing impaired families from Andhra Pradesh, South India. Materials and methods: Families in which the proband had prelingual, non-syndromic, sensorineural hearing loss and married to a partner who was either of normal hearing status (Deaf x Normal) or was also prelingual hearing impaired (Deaf x Deaf), with at least two generations of family members available for the study were enrolled and genomic DNA was extracted. Mitochondrial A1555G mutation in the 12SrRNA gene was screened by PCR-RFLP method and confirmed by direct sequencing of entire 12SrRNAgene 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: We screened twenty assortatively mating hearing impaired families comprising of one hundred and thirty seven members for A1555G mitochondrial DNA mutation and 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: This is the first report from India on the prevalence of A1555G mutation in normal hearing individuals. This study suggests 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 south Indian population. It would also be worthwhile to include screening for this mutation prior to aminoglycoside treatment in this population to avoid the preventable hearing loss.