Clinical and molecular study in a long-surviving patient with MLASA syndrome due to novel PUS1 mutations

• Published in: Neurogenetics Vol. 17; no. 1; pp. 65 - 70
• Main Authors: Cao, Michelangelo, Donà, Marta, Valentino, Lucia, Semplicini, Claudio, Maresca, Alessandra, Cassina, Matteo, Torraco, Alessandra, Galletta, Eva, Manfioli, Valeria, Sorarù, Gianni, Carelli, Valerio, Stramare, Roberto, Bertini, Enrico, Carozzo, Rosalba, Salviati, Leonardo, Pegoraro, Elena
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2016; Springer Nature B.V
• Subjects: Adult; Biomedical and Life Sciences; Biomedicine; Biosynthesis; Cardiomyopathy; DNA Mutational Analysis; Female; Genetic disorders; Human Genetics; Humans; Hydro-Lyases - chemistry; Hydro-Lyases - genetics; Magnetic Resonance Imaging; MELAS Syndrome - genetics; MELAS Syndrome - pathology; Mitochondrial DNA; Mitochondrial Myopathies - genetics; Mitochondrial Myopathies - pathology; Models, Molecular; Molecular Medicine; Mutation; Neurology; Neurosciences; Protein Conformation; Proteins; Short Communication; Survivors; Syndrome; MLASA; Mitochondrial biogenesis; mtDNA copy number; PUS1
• ISSN: 1364-6745; 1364-6753
• DOI: 10.1007/s10048-015-0465-x

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.