@article{62e4825693be4e4188dd4ecbecad3568,
title = "Splice Mutation in the Iron-Sulfur Cluster Scaffold Protein ISCU Causes Myopathy with Exercise Intolerance",
abstract = "A myopathy with severe exercise intolerance and myoglobinuria has been described in patients from northern Sweden, with associated deficiencies of succinate dehydrogenase and aconitase in skeletal muscle. We identified the gene for the iron-sulfur cluster scaffold protein ISCU as a candidate within a region of shared homozygosity among patients with this disease. We found a single mutation in ISCU that likely strengthens a weak splice acceptor site, with consequent exon retention. A marked reduction of ISCU mRNA and mitochondrial ISCU protein in patient muscle was associated with a decrease in the iron regulatory protein IRP1 and intracellular iron overload in skeletal muscle, consistent with a muscle-specific alteration of iron homeostasis in this disease. ISCU interacts with the Friedreich ataxia gene product frataxin in iron-sulfur cluster biosynthesis. Our results therefore extend the range of known human diseases that are caused by defects in iron-sulfur cluster biogenesis.",
author = "Fanny Mochel and Knight, {Melanie A.} and Tong, {Wing Hang} and Dena Hernandez and Karen Ayyad and Tanja Taivassalo and Andersen, {Peter M.} and Andrew Singleton and Rouault, {Tracey A.} and Fischbeck, {Kenneth H.} and Haller, {Ronald G.}",
note = "Funding Information: The authors wish to thank Nadine Romain, George Harmison, and Ian Rafferty for their help with the preparation of muscle tissues, the fibroblast culture, and the SNP-microarray genotyping, respectively, and Marguerite Gunder for invaluable assistance. We thank Drs. Karl G. Henriksson and Bjorn Lindvall for identifying and referring the patients. This work was supported by the intramural program of the National Institute of Neurological Disorders and Stroke, the National Institute on Aging, and the National Institute of Child Health and Human Development and by grants from the Muscular Dystrophy Association, the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH/NIAMS) (R01 AR050597), and a Veterans Affairs (VA) Merit Review (R.G.H.). M.A.K. was supported by a National Institute of Neurological Disorders and Stroke (NINDS) Competitive Postdoctoral Fellowship. ",
year = "2008",
month = mar,
day = "3",
doi = "10.1016/j.ajhg.2007.12.012",
language = "English (US)",
volume = "82",
pages = "652--660",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",
}