title: Clinical and molecular study in a long-surviving patient with MLASA syndrome due to novel PUS1 mutations.
abstract: Myopathy-lactic acidosis-sideroblastic anemia (MLASA) syndrome is a rare autosomal recessive disease. We studied a 43-year-old female presenting since childhood with mild cognitive impairment and sideroblastic anemia. She later developed hepatopathy, cardiomyopathy, and insulin-dependent diabetes. Muscle weakness appeared in adolescence and, at age 43, she was unable to walk. Two novel different mutations in the PUS1 gene were identified: c.487delA (p.I163Lfs*4) and c.884 G>A (p.R295Q). Quantitative analysis of DNA from skeletal muscle biopsies showed a significant increase in mitochondrial DNA (mtDNA) content in the patient compared to controls. Clinical and molecular findings of this patient widen the genotype-phenotype spectrum in MLASA syndrome.
authors.affiliation: Department of Neuroscience, University of Padova, Padua, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padua, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Donà
authors.affiliation: Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
authors.forename: M Lucia
authors.initials: ML
authors.lastname: Valentino
authors.affiliation: Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.|IRCCS Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Valentino
authors.affiliation: Department of Neuroscience, University of Padova, Padua, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Semplicini
authors.affiliation: IRCCS Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Maresca
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cassina
authors.affiliation: Unit for Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Children's Research Hospital "Bambino Gesù", IRCCS, Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Torraco
authors.affiliation: Department of Neuroscience, University of Padova, Padua, Italy.
authors.forename: Eva
authors.initials: E
authors.lastname: Galletta
authors.affiliation: Department of Neuroscience, University of Padova, Padua, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Manfioli
authors.affiliation: Department of Neuroscience, University of Padova, Padua, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Sorarù
authors.affiliation: Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.|IRCCS Institute of Neurological Sciences, Bellaria Hospital, Bologna, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.affiliation: Section of Radiology, Department of Medicine, University of Padova, Padua, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Stramare
authors.affiliation: Unit for Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Children's Research Hospital "Bambino Gesù", IRCCS, Rome, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Unit for Neuromuscular and Neurodegenerative Disorders, Laboratory of Molecular Medicine, Children's Research Hospital "Bambino Gesù", IRCCS, Rome, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Carrozzo
authors.affiliation: Department of Women's and Children's Health, University of Padova, Padua, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Salviati
authors.affiliation: Department of Neuroscience, University of Padova, Padua, Italy. elena.pegoraro@unipd.it.|Department of Neurosciences, University of Padova, via Giustiniani, 5, 35128, Padua, Italy. elena.pegoraro@unipd.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Pegoraro
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D006836:Hydro-Lyases / Q000737:chemistry / Q000235:genetics*; D017241:MELAS Syndrome / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000473:pathology; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017741:Survivors; D013577:Syndrome
chemical_list: D006836:Hydro-Lyases; C022479:pseudouridylate synthetase
keywords: MLASA; Mitochondrial biogenesis; PUS1; mtDNA copy number