CLINICAL REPORT Novel MTCYB Mutation in a Young Patient with Recurrent Stroke-like Episodes and Status Epilepticus Michelangelo Mancuso, 1 * Claudia Nesti, 2 Elena Caldarazzo Ienco, 1 Daniele Orsucci, 1 Chiara Pizzanelli, 1 Alberto Chiti, 1 Filippo S Giorgi, 1 Maria Chiara Meschini, 2 Gabriella Fontanini, 3 Filippo Maria Santorelli, 2 Annalisa Logerfo, 1 Alessandro Romano, 4 Gabriele Siciliano, 1 and Ubaldo Bonuccelli 1 1 Department of Experimental and Clinical Medicine, Neurological Clinic, University of Pisa, Via Roma 67, Pisa, Italy 2 Molecular Medicine, IRCCS Stella Maris, Pisa, Italy 3 Department of Surgery, Division of Pathological Anatomy, University of Pisa, Pisa, Italy 4 Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy Manuscript Received: 10 April 2014; Manuscript Accepted: 9 July 2014 The acronym “MELAS” (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) denotes patients with histological, biochemical and/or molecular evidence of mitochondrial disease who experience stroke-like episodes. Here we report on a girl with repeated stroke-like episodes and status epilepticus, who was diagnosed with MELAS due to a novel mitochondrial cytochrome b gene (MTCYB) mutation (m.15092G>A, which predicts p.G116S). Western blotting and in silico analyses suggested that this mutation could affect the stability of complex III. Cytochrome b is the only mtDNA- encoded subunit of respiratory chain complex III. Mutations in MTCYB have been associated with isolated mitochondrial myopathy and exercise intolerance, and rarely with multisystem and/or central nervous system involvement. If the m.3243A>G and other common MELAS mutations are absent in several tissues, MTCYB should be sequenced from muscle in patients with stroke-like episodes, especially if muscle histology does not support a mitochondrial myopathy and lactic acidosis is absent. Ó 2014 Wiley Periodicals, Inc. Key words: cytochrome b; genetics MELAS; mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes; mtDNA; stroke INTRODUCTION Stroke is the most common life-threatening neurological disease. It is a complex disorder resulting from the interplay of genetics and environment. In some instances (especially in young adults) stroke is the direct result of a monogenic disease. Here we report on a girl with repeated stroke-like episodes and status epilepticus, who at the end of a complex diagnostic work-up was diagnosed with mito- chondrial encephalomyopathy due to a novel mitochondrial cyto- chrome b gene (MTCYB) mutation. CLINICAL REPORT A 19-year-old Albanian girl was examined because of acute-onset of hemianopsia. Her past medical history was significant because of recurrent episodes of vomiting and abdominal pain since child- hood, migraine, slowness in learning at primary school, and episodic generalized seizures since age 13. Family history was unremarkable. Cranial MRI studies showed stroke-like lesions in the left tem- poro-parietal-occipital region associated with significant oedema How to Cite this Article: Mancuso M, Nesti C, Ienco EC, Orsucci D, Pizzanelli C, Chiti A, Giorgi FS, Meschini MC, Fontanini G, Santorelli FM, Logerfo A, Romano A, Siciliano G, Bonuccelli U. 2014. Novel MTCYB mutation in a young patient with recurrent stroke-like episodes and status epilepticus. Am J Med Genet Part A. 9999:1–4. Conflict of interest: The authors declare no conflicts of interest. Ã Correspondence to: Michelangelo Mancuso, M.D., PhD Department of Experimental and Clinical Medicine, Neurological Clinic, University of Pisa, Italy. E-mail: mancusomichelangelo@gmail.com Article first published online in Wiley Online Library (wileyonlinelibrary.com): 00 Month 2014 DOI 10.1002/ajmg.a.36725 Ó 2014 Wiley Periodicals, Inc. 1