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

J. H. Langdahl; M. Larsen; M. Frost; P. H. Andersen; K. B. Yderstræde; J. Vissing; M. Dunø; M. Thomassen; A. L. Frederiksen

doi:10.1111/cge.13201

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

J. H. Langdahl^*, M. Larsen, M. Frost, P. H. Andersen, K. B. Yderstræde, J. Vissing, M. Dunø, M. Thomassen, A. L. Frederiksen

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

6 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Clinical Genetics
Vol/bind	93
Udgave nummer	4
Sider (fra-til)	925-928
Antal sider	4
ISSN	0009-9163
DOI	https://doi.org/10.1111/cge.13201
Status	Udgivet - 2018

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10.1111/cge.13201

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

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.",

keywords = "heteroplasmy, m.3243A>G, MELAS, mitochondria",

author = "Langdahl, {J. H.} and M. Larsen and M. Frost and Andersen, {P. H.} and Yderstr{\ae}de, {K. B.} and J. Vissing and M. Dun{\o} and M. Thomassen and Frederiksen, {A. L.}",

year = "2018",

doi = "10.1111/cge.13201",

language = "English",

volume = "93",

pages = "925--928",

journal = "Clinical Genetics",

issn = "0009-9163",

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TY - JOUR

T1 - Lecocytes mutation load declines with age in carriers of the m.3243A>G mutation

T2 - A 10-year Prospective Cohort

AU - Langdahl, J. H.

AU - Larsen, M.

AU - Frost, M.

AU - Andersen, P. H.

AU - Yderstræde, K. B.

AU - Vissing, J.

AU - Dunø, M.

AU - Thomassen, M.

AU - Frederiksen, A. L.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - heteroplasmy

KW - m.3243A>G

KW - MELAS

KW - mitochondria

U2 - 10.1111/cge.13201

DO - 10.1111/cge.13201

M3 - Journal article

C2 - 29266179

AN - SCOPUS:85043976972

SN - 0009-9163

VL - 93

SP - 925

EP - 928

JO - Clinical Genetics

JF - Clinical Genetics

IS - 4

ER -

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

Abstract

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