Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population
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Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18–55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients’ blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.
KeywordsMitochondrion Ischemic stroke Young Diagnosis MELAS Mitochondrial disease Mutation
During this study, AS was funded by Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, European Research Council, University of Helsinki, and Academy of Finland. We are grateful to all study investigators and the core facility study team at the University of Rostock.
Compliance with ethical standards
The sifap1 study (http://www.sifap.eu/, NCT00414583) has been supported by an unrestricted scientific Grant from Shire Human Genetic Therapies to the University of Rostock.
Conflicts of interest
Ethics committee of the Medical Association Mecklenburg-Vorpommern (Board 2), University of Rostock, Rostock, Germany has approved this study on 14-SEPTEMBER-2006.
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