Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling

• Published in: Nature genetics Vol. 46; no. 2; pp. 188 - 193
• Main Authors: Logan, Clare V, Szabadkai, György, Sharpe, Jenny A, Parry, David A, Torelli, Silvia, Childs, Anne-Marie, Kriek, Marjolein, Phadke, Rahul, Johnson, Colin A, Roberts, Nicola Y, Bonthron, David T, Pysden, Karen A, Whyte, Tamieka, Munteanu, Iulia, Foley, A Reghan, Wheway, Gabrielle, Szymanska, Katarzyna, Natarajan, Subaashini, Abdelhamed, Zakia A, Morgan, Joanne E, Roper, Helen, Santen, Gijs W E, Niks, Erik H, van der Pol, W Ludo, Lindhout, Dick, Raffaello, Anna, De Stefani, Diego, den Dunnen, Johan T, Sun, Yu, Ginjaar, Ieke, Sewry, Caroline A, Hurles, Matthew, Rizzuto, Rosario, Duchen, Michael R, Muntoni, Francesco, Sheridan, Eamonn
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2014; Nature Publishing Group
• Subjects: 13/1; 13/51; 14/34; 45/22; 45/23; 631/208/1516; 692/308/2056; 692/699/375/374; 9/74; Agriculture; Analysis of Variance; Animal Genetics and Genomics; Base Sequence; Biomedical research; Biomedicine; Calcium Channels - metabolism; Calcium Signaling - genetics; Calcium Signaling - physiology; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cancer Research; Cation Transport Proteins - genetics; Cation Transport Proteins - metabolism; Cell culture; Cellular signal transduction; DNA, Complementary - genetics; Dystrophy; Exome - genetics; Extrapyramidal Tracts - pathology; Fluorescent Antibody Technique; Gene Function; Gene mutations; Genealogy; Genetic aspects; Health aspects; Histological Techniques; Human Genetics; Humans; Immunohistochemistry; Kinases; Learning Disabilities - genetics; letter; Medical research; Membrane Potential, Mitochondrial - genetics; Mitochondria; Mitochondria - metabolism; Mitochondrial Membrane Transport Proteins - genetics; Mitochondrial Membrane Transport Proteins - metabolism; Molecular Sequence Data; Movement Disorders - genetics; Muscle diseases; Muscular Diseases - genetics; Muscular dystrophy; Mutation; NMR; Nuclear magnetic resonance; Pedigree; Phenotype; Polymorphism, Single Nucleotide - genetics; Proteins; Quadriceps Muscle - pathology; Real-Time Polymerase Chain Reaction; Risk factors; Sequence Analysis, DNA; United Kingdom

Michael Duchen, Francesco Muntoni, Eamonn Sheridan and colleagues show that loss-of-function mutations in MICU1 cause a recessive disorder characterized by proximal myopathy, learning difficulties and progressive extrapyramidal motor deficits. The mutations alter mitochondrial calcium homeostasis, l...