TY  - JOUR
AU  - Kremer, Laura S
AU  - Distelmaier, Felix
AU  - Alhaddad, Bader
AU  - Hempel, Maja
AU  - Iuso, Arcangela
AU  - Küpper, Clemens
AU  - Mühlhausen, Chris
AU  - Kovacs-Nagy, Reka
AU  - Satanovskij, Robin
AU  - Graf, Elisabeth
AU  - Berutti, Riccardo
AU  - Eckstein, Gertrud
AU  - Durbin, Richard
AU  - Sauer, Sascha
AU  - Hoffmann, Georg F
AU  - Strom, Tim M
AU  - Santer, René
AU  - Meitinger, Thomas
AU  - Klopstock, Thomas
AU  - Prokisch, Holger
AU  - Haack, Tobias B
TI  - Bi-allelic Truncating Mutations in TANGO2 Cause Infancy-Onset Recurrent Metabolic Crises with Encephalocardiomyopathy.
JO  - The American journal of human genetics
VL  - 98
IS  - 2
SN  - 0002-9297
CY  - New York, NY
PB  - Elsevier
M1  - DZNE-2020-04710
SP  - 358-362
PY  - 2016
AB  - 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.
KW  - Alleles
KW  - Arrhythmias, Cardiac: diagnosis
KW  - Arrhythmias, Cardiac: genetics
KW  - Cardiomyopathies: diagnosis
KW  - Cardiomyopathies: genetics
KW  - Child, Preschool
KW  - Exome
KW  - Female
KW  - Humans
KW  - Infant
KW  - Male
KW  - Mitochondria: genetics
KW  - Mitochondria: metabolism
KW  - Mitochondrial Diseases: diagnosis
KW  - Mitochondrial Diseases: genetics
KW  - Mutation
KW  - Pedigree
LB  - PUB:(DE-HGF)16
C6  - pmid:26805782
C2  - pmc:PMC4746337
DO  - DOI:10.1016/j.ajhg.2015.12.009
UR  - https://pub.dzne.de/record/138388
ER  -