Pyruvate dehydrogenase deficiency: The relation of the E1α mutation to the E1β subunit deficiency
Year: 1996
Type: article
Study design: Case Report
Abstract: We report 7 patients with pyruvate dehydrogenase (PDH) deficiency caused by mutations of the PDH-E1 alpha subunit. Each patient had a different mutation; 4 with duplicate insertions, 1 with a deletion of tandem repeat, and 2 with point mutations. Five of the mutations were novel, thus confirming allelic heterogeneity. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in every patient. Pulse-labeling and chase study for the E1 alpha and E1 beta subunits revealed that initial synthesis of the mutant E1 alpha subunit was normal and posttranslational degradation was complete by 48 hours. However, the post-translational degradation rate of the E1 beta subunit varied from one patient to another. Factors other than instability of the E1 beta monomer must contribute to the degradation rate of this subunit in the presence of an E1 alpha subunit mutation. Including this series, 3 patients with the S312 deletion and 5 with the R302C point mutation have been reported, and all of these patients are female. These findings suggest that these two loci are hot spots for gene mutations, and may be lethal in the male fetus.
Source: Pediatric Neurology
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,520
OpenAlex ID: W2033090295