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Bi-allelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy

Item Type:Article
Title:Bi-allelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy
Creators Name:Kremer, L.S. and Distelmaier, F. and Alhaddad, B. and Hempel, M. and Iuso, A. and Küpper, C. and Mühlhausen, C. and Kovacs-Nagy, R. and Satanovskij, R. and Graf, E. and Berutti, R. and Eckstein, G. and Durbin, R. and Sauer, S. and Hoffmann, G.F. and Strom, T.M. and Santer, R. and Meitinger, T. and Klopstock, T. and Prokisch, H. and Haack, T.B.
Abstract:Molecular diagnosis of mitochondrial disorders is challenging because of extreme clinical and genetic heterogeneity. By exome sequencing, we identified three different bi-allelic truncating mutations in TANGO2 in three unrelated individuals with infancy-onset episodic metabolic crises characterized by encephalopathy, hypoglycemia, rhabdomyolysis, arrhythmias, and laboratory findings suggestive of a defect in mitochondrial fatty acid oxidation. Over the course of the disease, all individuals developed global brain atrophy with cognitive impairment and pyramidal signs. TANGO2 (transport and Golgi organization 2) encodes a protein with a putative function in redistribution of Golgi membranes into the endoplasmic reticulum in Drosophila and a mitochondrial localization has been confirmed in mice. Investigation of palmitate-dependent respiration in mutant fibroblasts showed evidence of a functional defect in mitochondrial β-oxidation. Our results establish TANGO2 deficiency as a clinically recognizable cause of pediatric disease with multi-organ involvement.
Keywords:Alleles, Cardiac Arrhythmias, Cardiomyopathies, Exome, Mitochondria, Mitochondrial Diseases, Mutation, Pedigree
Source:American Journal of Human Genetics
ISSN:0002-9297
Publisher:University of Chicago Press
Volume:98
Number:2
Page Range:358-362
Date:4 February 2016
Official Publication:https://doi.org/10.1016/j.ajhg.2015.12.009
PubMed:View item in PubMed

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