Longitudinal changes of mtDNA A3243G mutation load and level of functioning in MELAS.
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), one of the most common mitochondrial multisystemic diseases, is most commonly associated with an A-to-G transition at nucleotide position 3243 (A3243G) in mitochondrial DNA. We studied 34 individuals harboring the A3243G mutation for up to 7 years; 17 had the full MELAS phenotype and 17 who were classified as "carrier relatives" because they were either asymptomatic or had some symptoms suggestive of mitochondrial disease but no seizures or strokes. Using the sensitive real-time polymerase chain reaction to quantify the A3243G mutation, we confirmed that the percent mutation decreases progressively in DNA isolated from blood: the average percent decrease was 0.5% per year for fully symptomatic patients and 0.2% per year for oligosymptomatic carrier relatives. We also correlated mutant loads with functional status estimated by the Karnofksky score: even though the mutation load decreases, the level of functioning worsens in fully symptomatic patients, whereas the level of functioning of carrier relatives remains largely unchanged. This study suggests that A3243G mutant load in DNA isolated from blood is neither useful for prognosis nor for functional assessment.
Mehrazin
Mahsa
M
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Shanske
Sara
S
Kaufmann
Petra
P
Wei
Ying
Y
Coku
Jorida
J
Engelstad
Kristin
K
Naini
Ali
A
De Vivo
Darryl C
DC
DiMauro
Salvatore
S
D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D006801:Humans; D017567:Karnofsky Performance Status; D008137:Longitudinal Studies; D017241:MELAS Syndrome / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011379:Prognosis
D004272:DNA, Mitochondrial