Detection rates and phenotypic spectrum of m.3243A>G in the MT-TL1 gene: a molecular diagnostic laboratory perspective.
The nucleotide change A to G at position m.3243 in the mitochondrial tRNA leucine (UUR) gene (MT-TL1) is the most common point mutation reported in association with the Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes (MELAS) syndrome. Since the original description of this disorder, factors including random mitochondrial segregation and consequent variable tissue heteroplasmy are recognised to contribute to a much broader phenotypic spectrum associated with the MT-TL1 m.3243A>G mutation, often rendering the process of making a diagnosis complex. Reliance on clinicians' referral patterns means that for most molecular diagnostic laboratories, their positive identification rates for the common pathogenic mitochondrial DNA (mtDNA) mutations, including MT-TL1 m.3243A>G, is often relatively low compared to those reported in clinically targeted research studies. Herein, we report our results of consecutive prospective screening of 745 patients with a clinically suspected mitochondrial syndrome encompassing features associated with MT-TL1 m.3243A>G mutation.
St Vincent's Melbourne Neuromuscular Diagnostic Laboratory, Department of Clinical Neurosciences, Level 5 Daly Wing, St Vincent's Hospital, 35 Victoria Parade, Fitzroy, VIC 3065, Australia. Electronic address: judy.chin@svhm.org.au.
J
J
Chin
St Vincent's Melbourne Neuromuscular Diagnostic Laboratory, Department of Clinical Neurosciences, Level 5 Daly Wing, St Vincent's Hospital, 35 Victoria Parade, Fitzroy, VIC 3065, Australia.
R
R
Marotta
St Vincent's Melbourne Neuromuscular Diagnostic Laboratory, Department of Clinical Neurosciences, Level 5 Daly Wing, St Vincent's Hospital, 35 Victoria Parade, Fitzroy, VIC 3065, Australia.
M
M
Chiotis
St Vincent's Melbourne Neuromuscular Diagnostic Laboratory, Department of Clinical Neurosciences, Level 5 Daly Wing, St Vincent's Hospital, 35 Victoria Parade, Fitzroy, VIC 3065, Australia.
E H
EH
Allan
St Vincent's Melbourne Neuromuscular Diagnostic Laboratory, Department of Clinical Neurosciences, Level 5 Daly Wing, St Vincent's Hospital, 35 Victoria Parade, Fitzroy, VIC 3065, Australia. Electronic address: stevenjc@unimelb.edu.au.
S J
SJ
Collins
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D050259:Genes, Mitochondrial; D005820:Genetic Testing; D006801:Humans; D017241:MELAS Syndrome / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D015995:Prevalence; D012356:RNA, Transfer, Leu / Q000235:genetics*; D055815:Young Adult
D004272:DNA, Mitochondrial; D012356:RNA, Transfer, Leu
MELAS syndrome; Mitochondria; m.3243A>G point mutation; tRNA leucine