Abstract
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.
Highlights
Hypertrophic cardiomyopathy (HCM) is an inherited heart disease with a prevalence of 1:500 in the general population [1]
The distribution of the 446 variants among the mitochondrial DNA (mtDNA) genes is summarized in Table 2. 129 (28.9%) variants in non-coding regions and 183 (41.0%) synonymous variants were deselected, leaving 134 (30.0%) non-synonymous variants after first filtering step
We identified 446 different variants of which three, MT-TC: m.5772G>A, MT-TF: m.644A>G, and MT-CYB: m.15024G>A, p
Summary
Hypertrophic cardiomyopathy (HCM) is an inherited heart disease with a prevalence of 1:500 in the general population [1]. It is defined by hypertrophy of the left ventricle in the absence of other cardiac or systemic causes (e.g. systemic hypertension or aortic valve stenosis). More than 1400 mutations associated with HCM have been identified in 54 genes [1,4,5,6,7,8]. The majority of these genes encode sarcomere or PLOS ONE | DOI:10.1371/journal.pone.0124540. The majority of these genes encode sarcomere or PLOS ONE | DOI:10.1371/journal.pone.0124540 April 29, 2015
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