A Lethal Defect of Mitochondrial and Peroxisomal Fission
Hans R. Waterham, Ph.D., Janet Koster, B.Sc., Carlo W.T. van Roermund, Ph.D., Petra A.W. Mooyer, B.Sc., Ronald J.A. Wanders, Ph.D., and James V. Leonard, M.B., Ph.D.
We report on a newborn girl with microcephaly, abnormal braindevelopment, optic atrophy and hypoplasia, persistent lacticacidemia, and a mildly elevated plasma concentration of very-long-chainfatty acids. We found a defect of the fission of both mitochondriaand peroxisomes, as well as a heterozygous, dominant-negativemutation in the dynamin-like protein 1 gene (DLP1). The DLP1protein has previously been implicated, in vitro, in the fissionof both these organelles. Overexpression of the mutant DLP1in control cells reproduced the fission defect. Our findingsare representative of a class of disease characterized by defectsin both mitochondria and peroxisomes.
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From the Departments of Pediatrics (H.R.W., R.J.A.W.) and Clinical Chemistry (H.R.W., J.K., C.W.T.R., P.A.W.M., R.J.A.W.), Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam; and the Department of Pediatrics, Institute of Child Health, University College London, London (J.V.L.). Dr. Waterham and Ms. Koster contributed equally to this article.
Address reprint requests to Dr. Waterham at Laboratory Genetic Metabolic Diseases, Rm. F0-224, Department of Clinical Chemistry, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands, or at h.r.waterham{at}amc.uva.nl.
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