title: Mitochondrial DNA haplogroups and mutations in children with acquired central demyelination.
abstract: OBJECTIVE
  We investigated mitochondrial DNA (mtDNA) variants in children with a first episode of acquired demyelinating syndromes (PD-ADS) of the CNS and their relationship to disease phenotype, including subsequent diagnosis of multiple sclerosis (MS).
  
  
  METHODS
  This exploratory analysis included the initial 213 children with PD-ADS in the prospective Canadian Pediatric Demyelinating Study and 166 matched healthy sibling controls from the Canadian Autism Genome Project. A total of 31 single nucleotide polymorphisms (SNPs) were analyzed, including haplogroup-defining SNPs and mtDNA variants previously reported to be associated with MS.
  
  
  RESULTS
  Primary Leber hereditary optic neuropathy (LHON) mutations and other known pathogenic mtDNA mutations were absent in both patients with pediatric acquired demyelinating syndromes and controls. The 13708A haplogroup J-associated variant, previously linked to adult MS, was more frequent among subjects with PD-ADS (13.0%) compared to controls (6.2%; odds ratio [OR] 2.27; 95% confidence interval [CI] 1.06 to 4.83) and haplogroup M was associated with an earlier age at onset of PD-ADS (-1.74 years; 95% CI -3.33 to -0.07). In contrast, the haplogroup cluster UKJT, as well as 3 other SNPs, were each associated with a lower risk of PD-ADS. A total of 33 subjects with PD-ADS were diagnosed with MS during a mean follow-up period of 3.11 ± 1.14 (SD) years. No single SNP was associated with the risk of subsequent diagnosis of MS. However, haplogroup H was associated with an increased risk of MS (OR 2.60; 95% CI 1.21 to 5.55).
  
  
  CONCLUSIONS
  These data suggest an association between mtDNA variants and the risk of PD-ADS and of a subsequent MS diagnosis. Replication of these findings in an independent population of subjects with PD-ADS is required.
authors.affiliation: Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: S
authors.initials: S
authors.lastname: Venkateswaran
authors.forename: K
authors.initials: K
authors.lastname: Zheng
authors.forename: M
authors.initials: M
authors.lastname: Sacchetti
authors.forename: D
authors.initials: D
authors.lastname: Gagne
authors.forename: D L
authors.initials: DL
authors.lastname: Arnold
authors.forename: A D
authors.initials: AD
authors.lastname: Sadovnick
authors.forename: S W
authors.initials: SW
authors.lastname: Scherer
authors.forename: B
authors.initials: B
authors.lastname: Banwell
authors.forename: A
authors.initials: A
authors.lastname: Bar-Or
authors.forename: D K
authors.initials: DK
authors.lastname: Simon
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial