Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation.

Details

Serval ID
serval:BIB_29678
Type
Article: article from journal or magazin.
Publication sub-type
Case report (case report): feedback on an observation with a short commentary.
Collection
Publications
Institution
Title
Leigh syndrome due to compound heterozygosity of dihydrolipoamide dehydrogenase gene mutations. Description of the first E3 splice site mutation.
Journal
European Journal of Pediatrics
Author(s)
Grafakou O., Oexle K., van den Heuvel L., Smeets R., Trijbels F., Goebel H.H., Bosshard N., Superti-Furga A., Steinmann B., Smeitink J.
ISSN
0340-6199
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
162
Number
10
Pages
714-718
Language
english
Notes
Publication types: Case Reports ; Journal Article
Abstract
A boy with recurrent episodes of hypoglycaemia and ataxia, microcephaly, mental retardation, permanent lactic acidaemia, intermittent 2-oxoglutaric aciduria as well as elevation of serum branched chain amino acids was diagnosed with dihydrolipoamide dehydrogenase (E3) deficiency. Analysis of genomic DNA revealed compound heterozygosity for two novel mutations: I393T in exon 11, located at the interface domain of the protein and possibly interfering with its dimerisation, and IVS9+1G>A located at a consensus splice site. A heterozygous polymorphism was also detected. In the patient's cDNA the I393T mutation and the polymorphism appeared to be homozygous, indicating that the mRNA coming from the IVS9+1G>A mutant allele is not stable. CONCLUSION: as opposed to the non-neurological phenotype of patients with a homozygous G229C mutation, this patient developed Leigh syndrome. Dihydrolipoamide dehydrogenase and pyruvate dehydrogenase complex activities in muscle were 29% and 14% of the lowest control values, respectively. Pyruvate dehydrogenase complex activity in fibroblasts was normal, however, indicating that the biochemical examination of defects in energy metabolism should be performed in a more energy demanding tissue.
Keywords
Child, Preschool, Dihydrolipoamide Dehydrogenase/deficiency, Dihydrolipoamide Dehydrogenase/genetics, Fibroblasts/enzymology, Heterozygote, Humans, Leigh Disease/genetics, Male, Muscle, Skeletal/enzymology, Mutation, Missense, Pyruvate Dehydrogenase Complex/genetics, RNA Splice Sites
Pubmed
Web of science
Create date
19/11/2007 12:27
Last modification date
20/08/2019 13:09
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