title: Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.
abstract: 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.
authors.affiliation: Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Per Dubbsgatan 14, POB 430, 40530, Gothenburg, Sweden. turgut.tatlisumak@neuro.gu.se.|Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden. turgut.tatlisumak@neuro.gu.se.|Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. turgut.tatlisumak@neuro.gu.se.
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Putaala
authors.affiliation: Research Program for Molecular Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Innilä
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Enzinger
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Tiina M
authors.initials: TM
authors.lastname: Metso
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Curtze
authors.affiliation: Department of Neurology, Ernst-Moritz-Arndt University Medicine, Greifswald, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: von Sarnowski
authors.affiliation: Department of Neurology, Unidade Cerebrovascular Hospital de São José, Lisbon, Portugal.|Department of Neurology, Hospital Vila Franca de Xira, Vila Franca de Xira, Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Amaral-Silva
authors.affiliation: Department of Neurology, Charite University, Berlin, Germany.
authors.forename: Gerhard Jan
authors.initials: GJ
authors.lastname: Jungehulsing
authors.affiliation: Department of Neurology, University of Giessen, Giessen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Tanislav
authors.affiliation: Austin Health and Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, VIC, Australia.
authors.forename: Vincent
authors.initials: V
authors.lastname: Thijs
authors.affiliation: Albrecht-Kossel-Institute for Neuroregeneration, University of Rostock, Rostock, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Rolfs
authors.affiliation: Department of Clinical Neurosciences Neurology, Lund University, Lund, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Norrving
authors.affiliation: Department of Neurology, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Fazekas
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.|Research Program for Molecular Neurology, University of Helsinki, Helsinki, Finland.
authors.forename: Anu
authors.initials: A
authors.lastname: Suomalainen
authors.affiliation: Department of Neurology, New York University School of Medicine, New York, NY, USA.
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Kolodny
mesh_terms: D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D017241:MELAS Syndrome / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020521:Stroke / Q000235:genetics*; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial
keywords: Diagnosis; Ischemic stroke; MELAS; Mitochondrial disease; Mitochondrion; Mutation; Young