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: Michelangelo Cao, Marta Donà, M Lucia Valentino, Lucia Valentino, Claudio Semplicini, Alessandra Maresca, Matteo Cassina, Alessandra Torraco, Eva Galletta, Valeria Manfioli, Gianni Sorarù, Valerio Carelli, Roberto Stramare, Enrico Bertini, Rosalba Carrozzo, Leonardo Salviati, Elena Pegoraro
• Journal: Neurogenetics (Neurogenetics) Vol. 17 Issue 1 Pg. 65-70 (01 2016) ISSN: 1364-6753 [Electronic] United States
• PMID: 26556812 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydro-Lyases
• pseudouridylate synthetase

Topics

• Adult
• DNA Mutational Analysis
• Female
• Humans
• Hydro-Lyases (chemistry, genetics)
• MELAS Syndrome (genetics, pathology)
• Magnetic Resonance Imaging
• Mitochondrial Myopathies (genetics, pathology)
• Models, Molecular
• Mutation
• Protein Conformation
• Survivors
• Syndrome