ISSN:
1432-1203
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Medicine
Notes:
Abstract. Mutations in the glycine decarboxylase gene (GLDC) cause nonketotic hyperglycinemia (NKH), an inborn error of metabolism characterized by severe neurological disturbance. We have determined the structure of GLDC and of its pseudogene (ψ GLDC) and studied their expression for a molecular analysis of NKH. The GLDC gene spans at least 135 kb and consists of 25 exons. All donor and acceptor sites adhere to the canonical GT-AG rule, except for the donor site of intron 21, where a variant form GC is used instead of GT. The transcription initiation site has been assigned to a residue 163 bp upstream from the translation initiation triplet by primer extension analysis. The ψ GLDC gene has no intron and shares 97.5% homology with the coding region of functional GLDC, suggesting that ψ GLDC is a processed pseudogene that arose from the GLDC transcript about 4–8 million years ago. RNA blotting analysis has revealed that GLDC is expressed in human liver, kidney, brain, and placenta. We have also examined a patient with NKH with no detectable GLDC mRNA in his lymphoblasts. Exons 1–3 of the functional GLDC gene from this patient are not amplified by polymerase chain reaction (PCR), whereas those from control subjects are. These results suggest a large homozygous deletion (at least 30 kb) in the patient. Furthermore, we have devised a semi-quantitative PCR to estimate the number of GLDC alleles by using ψ GLDC as an internal control and have confirmed the homozygosity and heterozygosity of the deletion in the patient and his parents, respectively. Structural information of GLDC and ψ GLDC should facilitate the molecular analysis of NKH.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004390000250
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