Journal article
MECR Mutations Cause Childhood-Onset Dystonia and Optic Atrophy, a Mitochondrial Fatty Acid Synthesis Disorder
G Heimer, JM Kerätär, LG Riley, S Balasubramaniam, E Eyal, LP Pietikäinen, JK Hiltunen, D Marek-Yagel, J Hamada, A Gregory, C Rogers, P Hogarth, MA Nance, N Shalva, A Veber, M Tzadok, A Nissenkorn, D Tonduti, F Renaldo, MJ Bamshad Show all
American Journal of Human Genetics | CELL PRESS | Published : 2016
Abstract
Mitochondrial fatty acid synthesis (mtFAS) is an evolutionarily conserved pathway essential for the function of the respiratory chain and several mitochondrial enzyme complexes. We report here a unique neurometabolic human disorder caused by defective mtFAS. Seven individuals from five unrelated families presented with childhood-onset dystonia, optic atrophy, and basal ganglia signal abnormalities on MRI. All affected individuals were found to harbor recessive mutations in MECR encoding the mitochondrial trans-2-enoyl-coenzyme A-reductase involved in human mtFAS. All six mutations are extremely rare in the general population, segregate with the disease in the families, and are predicted to b..
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Awarded by National Heart, Lung, and Blood Institute
Funding Acknowledgements
The authors would like to acknowledge the families for their collaboration. The Israeli group was supported by funds from the Israel Science Foundation (grant number 2023/14) and the Pinchas Borenstein Talpiot Medical Leadership Program. The Finnish group was supported by the Sigrid Juselius Foundation and the Academy of Finland. The American group was funded by the NBIA Disorders Association and by philanthropic support. Sequencing for the American group was provided by the University of Washington Center for Mendelian Genomics (UW-CMG) and was funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute grant 2UM1HG006493 to Drs. Debbie Nickerson, Michael Bamshad, and Suzanne Leal. The Australian group was supported by a New South Wales Office of Health and Medical Research Council Sydney Genomics Collaborative grant (J.C. and L.G.R.), NHMRC project grant 1026891 (J.C.), Cancer Institute NSW fellowship 13/ECF/1-46 (M.J.C.), and generous financial support from the Kinghorn Foundation. J.C. is also grateful to the Crane and Perkins families for their generous financial support. The Italian group was supported by Pierfranco and Luisa Mariani Foundation. They also thank the Cell lines and DNA Bank of Paediatric Movement Disorders and Mitochondrial Diseases of the Telethon Genetic Biobank Network, which is supported by TELETHON Italy (project no. GTB09003) and the Bank for the Diagnosis and Research of Movement Disorders (MDB) of the EuroBiobank.