Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM. Several polymorphic mtDNA variants are associated with a variety of late-onset degenerative diseases and affect mitochondrial function. We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM. In 87 Danish HCM patients, full mtDNA sequencing revealed 446 variants. After elimination of 312 (69.9%) non-coding and synonymous variants, a further 109 (24.4%) with a global prevalence > 0.1%, three (0.7%) haplogroup associated and 19 (2.0%) variants with a low predicted in silico likelihood of pathogenicity, three variants: MT-TC: m.5772G>A, MT-TF: m.644A>G, and MT-CYB: m.15024G>A, p.C93Y remained. A detailed analysis of these variants indicated that none of them are likely to cause HCM. In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM.
Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Christian M
CM
Hagen
Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Frederik H
FH
Aidt
Department of Cardiology, Roskilde Hospital, Roskilde, Denmark.
Ole
O
Havndrup
Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Paula L
PL
Hedley
Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark.
Morten K
MK
Jensen
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jørgen K
JK
Kanters
Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark.
Tam T
TT
Pham
Department of Medicine B, The Heart Center, Rigshospitalet, Copenhagen, Denmark.
Henning
H
Bundgaard
Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Michael
M
Christiansen
D000328:Adult; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics*; D003718:Denmark; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
D004272:DNA, Mitochondrial