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Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy.

Hagen CM, Aidt FH, Havndrup O, Hedley PL, Jensen MK, Kanters JK, Pham TT, Bundgaard H, Christiansen M - PLoS ONE (2015)

Bottom Line: We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM.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.In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM.

View Article: PubMed Central - PubMed

Affiliation: Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

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.

No MeSH data available.


Related in: MedlinePlus

The algorithm used to select for potentially pathogenic mtDNA variants.
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pone.0124540.g001: The algorithm used to select for potentially pathogenic mtDNA variants.

Mentions: In order to identify potential HCM associated mtDNA variants we performed a multi-step selection procedure as depicted in Fig 1. In the first step synonymous and non-coding variants were identified using MitoMaster (www.mitomap.org/MITOMASTER) and removed. In step two, the global allele frequencies were obtained using MitoMaster and GenBank (www.ncbi.nlm.nih.gov/genbank/) and variants with a frequency >0.1% were removed. In step three, any haplogroup association for remaining variants was established using PhyloTree Build 16 (Feb 2014) [47] and they were removed if they were part of the variants defining the mtDNA haplogroup of the patient. Thereafter, mtDNA variants in protein and RNA coding genes were evaluated separately.


Private mitochondrial DNA variants in danish patients with hypertrophic cardiomyopathy.

Hagen CM, Aidt FH, Havndrup O, Hedley PL, Jensen MK, Kanters JK, Pham TT, Bundgaard H, Christiansen M - PLoS ONE (2015)

The algorithm used to select for potentially pathogenic mtDNA variants.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414448&req=5

pone.0124540.g001: The algorithm used to select for potentially pathogenic mtDNA variants.
Mentions: In order to identify potential HCM associated mtDNA variants we performed a multi-step selection procedure as depicted in Fig 1. In the first step synonymous and non-coding variants were identified using MitoMaster (www.mitomap.org/MITOMASTER) and removed. In step two, the global allele frequencies were obtained using MitoMaster and GenBank (www.ncbi.nlm.nih.gov/genbank/) and variants with a frequency >0.1% were removed. In step three, any haplogroup association for remaining variants was established using PhyloTree Build 16 (Feb 2014) [47] and they were removed if they were part of the variants defining the mtDNA haplogroup of the patient. Thereafter, mtDNA variants in protein and RNA coding genes were evaluated separately.

Bottom Line: We examined the role of private, non-haplogroup associated, mitochondrial variants in the etiology of HCM.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.In conclusion, private mtDNA mutations are frequent, but they are rarely, if ever, associated with HCM.

View Article: PubMed Central - PubMed

Affiliation: Department of Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

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.

No MeSH data available.


Related in: MedlinePlus