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

• Verfasst von: Kremer, Laura S. [VerfasserIn]
• Verfasst von: Hoffmann, Georg Friedrich [VerfasserIn]
• Titel: Bi-allelic truncating mutations in TANGO2 cause infancy-onset recurrent metabolic crises with encephalocardiomyopathy
• Verf.angabe: Laura S. Kremer, Felix Distelmaier, Bader Alhaddad, Maja Hempel, Arcangela Iuso, Clemens Küpper, Chris Mühlhausen, Reka Kovacs-Nagy, Robin Satanovskij, Elisabeth Graf, Riccardo Berutti, Gertrud Eckstein, Richard Durbin, Sascha Sauer, Georg F. Hoffmann, Tim M. Strom, René Santer, Thomas Meitinger, Thomas Klopstock, Holger Prokisch, and Tobias B. Haack
• E-Jahr: 2016
• Jahr: January 21, 2016
• Umfang: 5 S.
• Fussnoten: Gesehen am 20.11.2019
• Titel Quelle: Enthalten in: The American journal of human genetics
• Ort Quelle: New York, NY [u.a.] : Cell Press, 1949
• Jahr Quelle: 2016
• Band/Heft Quelle: 98(2016), 2, Seite 358-362
• ISSN Quelle: 1537-6605
• DOI: doi:10.1016/j.ajhg.2015.12.009
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1682234231

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.