title: Genetic Epidemiology of Mitochondrial Pathogenic Variants Causing Nonsyndromic Hearing Loss in a Large Cohort of South Indian Hearing Impaired Individuals.
abstract: Mitochondria play a critical role in the generation of metabolic energy in the form of ATP. Tissues and organs that are highly dependent on aerobic metabolism are involved in mitochondrial disorders including nonsyndromic hearing loss (NSHL). Seven pathogenic variants leading to NSHL have so far been reported on two mitochondrial genes: MT-RNR1 encoding 12SrRNA and MT-TS1 encoding tRNA for Ser((UCN)) . We screened 729 prelingual NSHL subjects to determine the prevalence of MT-RNR1 variants at position m.961, m.1555A>G and m.1494C>T, and MT-TS1 m.7445A>G, m.7472insC m.7510T>C and m.7511T>C variants. Mitochondrial pathogenic variants were found in eight probands (1.1%). Five of them were found to have the m.1555A>G variant, two others had m.7472insC and one proband had m.7444G>A. The extended relatives of these probands showed variable degrees of hearing loss and age at onset. This study shows that mitochondrial pathogenic alleles contribute to about 1% prelingual hearing loss. This study will henceforth provide the reference for the prevalence of mitochondrial pathogenic alleles in the South Indian population, which to date has not been estimated. The m.1555A>G variant is a primary predisposing genetic factor for the development of hearing loss. Our study strongly suggests that mitochondrial genotyping should be considered for all hearing impaired individuals and particularly in families where transmission is compatible with maternal inheritance, after ruling out the most common variants.
authors.affiliation: Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
authors.forename: Mahalingam
authors.initials: M
authors.lastname: Subathra
authors.affiliation: Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
authors.forename: Arabandi
authors.initials: A
authors.lastname: Ramesh
authors.affiliation: Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
authors.forename: Mathiyalagan
authors.initials: M
authors.lastname: Selvakumari
authors.affiliation: DOAST (Doctrine Oriented Art of Symbiotic Treatment) Hearing Care Center and Integrated Therapy Center for Autism, Anna Nagar West, Chennai, India.
authors.forename: N P
authors.initials: NP
authors.lastname: Karthikeyen
authors.affiliation: Department of Genetics, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, India.
authors.forename: C R Srikumari
authors.initials: CR
authors.lastname: Srisailapathy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003638:Deafness / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D050259:Genes, Mitochondrial; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D017720:Molecular Epidemiology; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012335:RNA, Ribosomal / Q000235:genetics; D012362:RNA, Transfer, Ser / Q000235:genetics; D055815:Young Adult
chemical_list: D012335:RNA, Ribosomal; D012362:RNA, Transfer, Ser; C075526:RNA, ribosomal, 12S
keywords: Nonsyndromic hearing loss; Prelingual; age at onset; mitochondrial pathogenic alleles; pure-tone-audiometry; variable severity