Adenine nucleotide translocator 1 deficiency associated with Sengers syndrome.
Sengers syndrome is characterized by congenital cataracts, hypertrophic cardiomyopathy, mitochondrial myopathy, and lactic acidosis, but no abnormalities have been found with routine mitochondrial biochemical diagnostics (the determination of pyruvate oxidation rates and enzyme measurements). In immunoblot analysis, the protein content of the mitochondrial adenine nucleotide translocator 1 (ANT1) was found to be strongly reduced in the muscle tissues of two unrelated patients with Sengers syndrome. In addition, low residual adenine nucleotide translocator activity was detected upon the reconstitution of detergent-solubilized mitochondrial extracts from the patients' skeletal or heart muscle into liposomes. Sequence analysis and linkage analysis showed that ANT1 was not the primary genetic cause of Sengers syndrome. We propose that transcriptional, translational, or posttranslational events are responsible for the ANT1 deficiency associated with the syndrome.
Jordens
Eric Z
EZ
Department of Pediatrics, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Palmieri
Luigi
L
Huizing
Marjan
M
van den Heuvel
Lambert P
LP
Sengers
Rob C A
RC
Dörner
Andrea
A
Ruitenbeek
Wim
W
Trijbels
Frans J
FJ
Valsson
Jullius
J
Sigfusson
Gunnlaugur
G
Palmieri
Ferdinando
F
Smeitink
Jan A M
JA
D001692:Biological Transport / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006801:Humans; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology; D000226:Mitochondrial ADP, ATP Translocases / Q000172:deficiency* / Q000235:genetics*; D017240:Mitochondrial Myopathies / Q000201:enzymology* / Q000235:genetics*; D009206:Myocardium / Q000201:enzymology; D010375:Pedigree; D013577:Syndrome
D000226:Mitochondrial ADP, ATP Translocases