Abstract |
Five cases of glycerol kinase deficiency are presented with clinical, biochemical, and genetic results. Two had the glycerol kinase deficiency as part of an Xp21 contiguous gene deletion syndrome-complex form-and three had an isolated form of the enzyme deficiency. In these we found two splice site mutations (IVS1+4A>G, IVS9-1G>T) and one insertion (1393_1394insG). In patients with the complex form, a deletion of the DAX1, GK genes and the distal part of the DMD gene was found. A computerized study was performed to predict the effects of the splice site mutations. It showed that the IVS9-1G>T mutation substantially altered and removed the wild-type site and enhanced a cryptic site seven nucleotides downstream, and that the IVS1+4A>G diminished the strength of the wild-type donor site from strong to leaky. To verify these predictions, we developed an RT-PCR system with gene-specific primers that exclusively amplifies the Xp21 glycerol kinase gene transcript. Identification of individuals at risk is motivated by a need to avoid delay in a correct diagnosis. For reliable identification of heterozygotes for isolated glycerol kinase deficiency, knowledge of the specific mutation in the proband is required. This is easily obtained with the RT-PCR analyses developed in this study.
|
Authors | Christina Hellerud, Maciej Adamowicz, Dorota Jurkiewicz, Joanna Taybert, Jolanta Kubalska, Elzbieta Ciara, Ewa Popowska, James R Ellis, Sven Lindstedt, Ewa Pronicka |
Journal | Molecular genetics and metabolism
(Mol Genet Metab)
Vol. 79
Issue 3
Pg. 149-59
(Jul 2003)
ISSN: 1096-7192 [Print] United States |
PMID | 12855219
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- DAX-1 Orphan Nuclear Receptor
- DNA Primers
- DNA-Binding Proteins
- NR0B1 protein, human
- RNA, Messenger
- Receptors, Retinoic Acid
- Repressor Proteins
- Glycerol Kinase
- Glycerol
|
Topics |
- Adrenal Insufficiency
(genetics)
- Chromosomes, Human, X
- DAX-1 Orphan Nuclear Receptor
- DNA Mutational Analysis
- DNA Primers
(chemistry)
- DNA-Binding Proteins
(chemistry, deficiency, genetics)
- Gene Deletion
- Glycerol
(blood, urine)
- Glycerol Kinase
(chemistry, deficiency, genetics)
- Humans
- Infant, Newborn
- Male
- Molecular Sequence Data
- Muscular Dystrophy, Duchenne
(genetics)
- Mutation
- Poland
- Polymorphism, Single-Stranded Conformational
- RNA, Messenger
(genetics, metabolism)
- Receptors, Retinoic Acid
(chemistry, deficiency, genetics)
- Repressor Proteins
(chemistry, genetics)
- Reverse Transcriptase Polymerase Chain Reaction
(methods)
|