Research in Otolaryngology 2014, 3(1): 1-7 DOI: 10.5923/j.otolaryn.20140301.01 Is Screening for Mitochondrial A1555G Mutation among Assortative Mating Hearing Impaired Families Important? : A Prefatory Quest Amritkumar Pavithra, Pallikarana Tirumala Harini, Jayasankaran Chandru, Chodisetty Sarvani, Akanksha Rastogi, Mathiyalagan Selvakumari, Mahalingam Subathra, Arabandi Ramesh, C. R. Srikumari Srisailapathy * Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India Abstract 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. Keywords A1555G mutation, Assortative mating, Hearing loss, India, 12SrRNA 1. Introduction Profound hearing loss is the most frequent sensory disorder affecting at least one in 500 newborns worldwide[1]. Hearing loss (HL) is genetically heterogeneous and has variety of clinical presentations. It is estimated that over 50% of HL has genetic predisposition, while 20-25% is due to identifiable environmental factors which include prenatal or perinatal viral infections, especially cytomegalovirus infection, acoustic or cerebral trauma leading to cochlear damage or ototoxic drugs such as antibiotics, and the remaining 25-30% of HL is of unknown etiology. Among the * Corresponding author: srikumaripavithra@gmail.com (C. R. Srikumari Srisailapathy) Published online at http://journal.sapub.org/otolaryn Copyright © 2014 Scientific & Academic Publishing. All Rights Reserved genetic causes, autosomal recessive inheritance accounts for about 80% of HL, followed by about 20% due to autosomal dominant inheritance, while X-linked inheritance and mitochondrial inheritance contribute to about 1% of HL each[2-4]. Several mutations in the mitochondrial DNA (mtDNA) have been found to be associated with syndromic, non-syndromic and aminoglycoside-induced hearing loss. The role of mtDNA mutations in non-syndromic hearing loss (NSHL) is either as a primary or as a predisposing factor. Hearing loss can be due to inherited, acquired, heteroplasmic or homoplasmic mtDNA mutations[5]. According to MITOMAP[6], till date, the pathogenicity of four mt DNA mutations has been clearly established in NSHL: C1494T and A1555G, located in the 12S ribosomal RNA gene (MTRNR1, MIM 561000) and A7445G and T7511C, located in the ser (UCN) transfer RNAgene (MTTS1, MIM 590080).