Mutation Load of Single, Large-Scale Deletions of mtDNA in Mitotic and Postmitotic Tissues
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Mutation Load of Single, Large-Scale Deletions of mtDNA in Mitotic and Postmitotic Tissues. / Jeppesen, Tina D.; Duno, Morten; Vissing, John.
I: Frontiers in Genetics, Bind 11, 547638, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Mutation Load of Single, Large-Scale Deletions of mtDNA in Mitotic and Postmitotic Tissues
AU - Jeppesen, Tina D.
AU - Duno, Morten
AU - Vissing, John
PY - 2020
Y1 - 2020
N2 - It is generally accepted that patients with chronic progressive ophthalmoplegia caused by single large-scale deletion (SLD) of mitochondrial DNA (mtDNA) only harbor mutation in skeletal and eye muscles. The aim of this study was to investigate the presence and the level of heteroplasmy of mtDNA deletions in mitotic tissues of patients displaying mtDNA deletion of mitotic tissues in patients with SLDs and pure muscle phenotype. MtDNA mutation load was studied in three mitotic (urine epithelial cells, buccal mucosa, and blood) and one postmitotic (skeletal muscle) tissues in 17 patients with SLDs of mtDNA and pure muscle involvement. All patients had mtDNA deletion in skeletal muscle, and 78% of the patients also displayed the mtDNA deletion in mitotic tissues. The mtDNA mutation load was higher in skeletal muscle versus mitotic tissues. The mtDNA mutation load did not correlate with age of sampling of tissues, but there was a correlation between the mtDNA mutations load in skeletal muscle and (1) the site of 5′ end breaking point of the SLD, (2) the size of SLD, (3) the number of affected tRNAs, and (4) age at onset (r > 0.58, P < 0.05). The findings indicate that mtDNA mutation in mitotic tissue is common in patients with SLDs of mtDNA. The lack of correlation between age of tissue sampling, age at onset, and mtDNA mutation load in mitotic tissues indicates that there is no extensive post-natal modification of mtDNA mutation load in mitotic tissues of patients with pure muscle phenotype.
AB - It is generally accepted that patients with chronic progressive ophthalmoplegia caused by single large-scale deletion (SLD) of mitochondrial DNA (mtDNA) only harbor mutation in skeletal and eye muscles. The aim of this study was to investigate the presence and the level of heteroplasmy of mtDNA deletions in mitotic tissues of patients displaying mtDNA deletion of mitotic tissues in patients with SLDs and pure muscle phenotype. MtDNA mutation load was studied in three mitotic (urine epithelial cells, buccal mucosa, and blood) and one postmitotic (skeletal muscle) tissues in 17 patients with SLDs of mtDNA and pure muscle involvement. All patients had mtDNA deletion in skeletal muscle, and 78% of the patients also displayed the mtDNA deletion in mitotic tissues. The mtDNA mutation load was higher in skeletal muscle versus mitotic tissues. The mtDNA mutation load did not correlate with age of sampling of tissues, but there was a correlation between the mtDNA mutations load in skeletal muscle and (1) the site of 5′ end breaking point of the SLD, (2) the size of SLD, (3) the number of affected tRNAs, and (4) age at onset (r > 0.58, P < 0.05). The findings indicate that mtDNA mutation in mitotic tissue is common in patients with SLDs of mtDNA. The lack of correlation between age of tissue sampling, age at onset, and mtDNA mutation load in mitotic tissues indicates that there is no extensive post-natal modification of mtDNA mutation load in mitotic tissues of patients with pure muscle phenotype.
KW - chronic progressive external ophthalmoplegia
KW - CPEO
KW - mitochondrial myopathy
KW - mtDNA deletion
KW - mtDNA mutation
KW - phenotype–genotype
U2 - 10.3389/fgene.2020.547638
DO - 10.3389/fgene.2020.547638
M3 - Journal article
C2 - 33133144
AN - SCOPUS:85092937755
VL - 11
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
M1 - 547638
ER -
ID: 256165465