title: Haplogroup heterogeneity of LHON patients carrying the m.14484T>C mutation in India.
abstract: OBJECTIVE
  To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber hereditary optic neuropathy (LHON) patients carrying the m.14484T>C mutation.
  
  
  METHODS
  Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants.
  
  
  RESULTS
  In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male: female = 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e., F1c1, M31a, U2a, M*, I1, M6, M3a1, and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON.
  
  
  CONCLUSIONS
  Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Nahid Akhtar
authors.initials: NA
authors.lastname: Khan
authors.forename: Periyasamy
authors.initials: P
authors.lastname: Govindaraj
authors.forename: Nagasamy
authors.initials: N
authors.lastname: Soumittra
authors.forename: Sundaramoorthy
authors.initials: S
authors.lastname: Srilekha
authors.forename: Selvakumar
authors.initials: S
authors.lastname: Ambika
authors.forename: Ayyasamy
authors.initials: A
authors.lastname: Vanniarajan
authors.forename: Angamuthu K
authors.initials: AK
authors.lastname: Meena
authors.forename: Megha S
authors.initials: MS
authors.lastname: Uppin
authors.forename: Challa
authors.initials: C
authors.lastname: Sundaram
authors.forename: Arun B
authors.initials: AB
authors.lastname: Taly
authors.forename: Parayil Sankaran
authors.initials: PS
authors.lastname: Bindu
authors.forename: Narayanappa
authors.initials: N
authors.lastname: Gayathri
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D019143:Evolution, Molecular; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D009245:NADH Dehydrogenase / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010802:Phylogeny; D017354:Point Mutation / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C507225:MT-ND6 protein, human; D009245:NADH Dehydrogenase
keywords: LHON; haplogroup; m.14484T>C; mtDNA; mutations