Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy

Research output: Contribution to journalJournal articleResearchpeer-review

Christian M Hagen, Frederik H Aidt, Ole Havndrup, Paula L Hedley, Morten K Jensen, Jørgen K Kanters, Tam T Pham, Henning Bundgaard, Michael Christiansen

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.

Original languageEnglish
Article numbere0124540
JournalPLOS ONE
Volume10
Issue number4
Pages (from-to)1-15
Number of pages15
ISSN1932-6203
DOIs
Publication statusPublished - 2015

ID: 140432804