GRACILE Syndrome, a Lethal Metabolic Disorder with Iron
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Am. J. Hum. Genet. 71:863–876, 2002 GRACILE Syndrome, a Lethal Metabolic Disorder with Iron Overload, Is Caused by a Point Mutation in BCS1L Ilona Visapa¨a¨,1,3 Vineta Fellman,7 Jouni Vesa,1 Ayan Dasvarma,8 Jenna L. Hutton,2 Vijay Kumar,5 Gregory S. Payne,2 Marja Makarow,5 Rudy Van Coster,9 Robert W. Taylor,10 Douglass M. Turnbull,10 Anu Suomalainen,6 and Leena Peltonen1,3,4 Departments of 1Human Genetics and 2Biological Chemistry, University of California Los Angeles School of Medicine, Los Angeles; 3Department of Molecular Medicine, National Public Health Institute, 4Department of Medical Genetics, 5Institute of Biotechnology, and 6Department of Neurology and Programme of Neurosciences, University of Helsinki, and 7Hospital for Children and Adolescents, Helsinki University Central Hospital, Helsinki; 8Murdoch Children’s Research Institute, Melbourne, Australia; 9Department of Pediatrics, Ghent University Hospital, Ghent, Belgium; and 10Department of Neurology, University of Newcastle upon Tyne, Newcastle, United Kingdom GRACILE (growth retardation, aminoaciduria, cholestasis, iron overload, lactacidosis, and early death) syndrome is a recessively inherited lethal disease characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. We previously localized the causative gene to a 1.5-cM region on chromosome 2q33-37. In the present study, we report the molecular defect causing this metabolic disorder, by identifying a homozygous missense mutation that results in an S78G amino acid change in the BCS1L gene in Finnish patients with GRACILE syndrome, as well as five different mutations in three British infants.
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