title: Complete mitochondrial genome analysis and clinical documentation of a five-generational Indian family with mitochondrial 1555A>G mutation and postlingual hearing loss.
abstract: Hearing loss is the most common sensory disorder and is genetically heterogeneous. Apart from nuclear gene mutations, a number of inherited mitochondrial mutations have also been implicated. The m.1555A>G mutation in the mitochondrial MT-RNR1 gene is reported as the most common mutation causing nonsyndromic hearing loss in various ethnic populations. We report here for the first time the clinical, genetic and molecular characterisation of a single large five-generational Tamil-speaking South Indian family with maternally inherited nonsyndromic postlingual hearing loss. Molecular analysis led to identification of m.1555A>G in 28 maternal relatives with variable degree of phenotypic expression. The penetrance of hearing loss among the maternal relatives in this family was 55%. Sequence analysis of the complete mitochondrial genome in 36 members of this pedigree identified 25 known variants and one novel variant co-transmitted along with m.1555A>G mutation. The mtDNA haplotype analysis revealed that the maternal relatives carry the R*T2 haplotype similar to Europeans and South Asians. Sequencing of the coding exon of GJB2 nuclear gene did not show any pathogenic mutations. The results suggest that other nuclear or environmental modifying factors could have played a role in the differential expression of mutation m.1555A>G in postlingual hearing loss in this family.
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.forename: Mathiyalagan
authors.initials: M
authors.lastname: Selvakumari
authors.forename: Arabandi
authors.initials: A
authors.lastname: Ramesh
authors.forename: Rajagopalan
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Kalpita Rashmi
authors.initials: KR
authors.lastname: Karan
authors.forename: Manpreet
authors.initials: M
authors.lastname: Kaur
authors.forename: Mayakannan
authors.initials: M
authors.lastname: Manikandan
authors.forename: C R
authors.initials: CR
authors.lastname: Srikumari Srisailapathy
mesh_terms: D001483:Base Sequence; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D054629:Genome, Mitochondrial / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D034381:Hearing Loss / Q000235:genetics*; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation / Q000235:genetics*; D012335:RNA, Ribosomal / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D017630:Connexins; D017931:DNA Primers; C000607042:GJB2 protein, human; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000072259:Connexin 26
keywords: Postlingual hearing loss; haplogroups; m.1555A>G mutation; mitochondrial genome; penetrance; pure-tone audiometry; variable severity