Lecocytes mutation load declines with age in carriers of the m.3243A>G mutation: A 10-year Prospective Cohort

Jakob Høgild Langdahl, Martin Larsen, Morten Frost, Per Heden Andersen, Knud Bonnet Yderstraede, John Vissing, Morten Dunø, Mads Thomassen, Anja Lisbeth Frederiksen

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Abstract

Carriers of the mitochondrial mutation m.3243A>G presents highly variable phenotypes including mitochondrial encephalomyopathy, lactoacidosis and stroke-like episodes (MELAS). We conducted a follow-up study to evaluate changes in leucocyte heteroplasmy and the clinical phenotypes in m.3243A>G carriers. Leucocyte heteroplasmy was determined by next generation sequencing covered by 100 000X reads in 32 individuals with a median follow-up of 10.2 years. Ten-year clinical follow-up is reported in 46 individuals. The annual leucocyte mutation level declined by −0.7 (±0.4) percentage points/year (P <.0001), and correlated with the level of the initial sample (ρ = −0.92, P <.0001). Eleven of 46 m.3243A>G carriers died and clinical symptoms progressed. This longitudinal study shows the decline in leucocyte m.3243A>G heteroplasmy associates with the level of the initial sample. Further, there was a high mortality among carriers.

Original languageEnglish
JournalClinical Genetics
Volume93
Issue number4
Pages (from-to)925-928
ISSN0009-9163
DOIs
Publication statusPublished - Apr 2018

Keywords

  • MELAS
  • heteroplasmy
  • m.3243A>G
  • mitochondria

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