Molecular analysis of porphobilinogen (PBG) deaminase gene mutations in acute intermittent porphyria: first study in patients of Slavic origin

Acute intermittent porphyria (AIP) is an autosomally dominant inherited metabolic disorders caused by decreased activity of porphobilinogen deaminase, the third enzyme in the human heme biosynthetic pathway. We report here the first mutations in the human porphobilinogen deaminase gene in seven unre...

Full description

Saved in:
Bibliographic Details
Published in:Scandinavian journal of clinical and laboratory investigation 1997, Vol.57 (3), p.217-224
Main Authors: Rosipal, R., Puy, H., Lamoril, J., Martasek, P., Nordmann, Y., Deybach, J. C.
Format: Article
Language:English
Subjects:
Aminolevulinic Acid - urine
Biological and medical sciences
Czech Republic
denaturing gradient gel electrophoresis
Exons
Genetic Testing
Humans
Hydroxymethylbilane Synthase - blood
Hydroxymethylbilane Synthase - genetics
Introns
Medical sciences
Metabolic diseases
Mutation
Other metabolic disorders
Pigments (porphyrias, hyperbilirubinemias...)
Porphobilinogen - urine
porphobilinogen deaminase
porphyria
Porphyria, Acute Intermittent - blood
Porphyria, Acute Intermittent - genetics
Porphyria, Acute Intermittent - urine
Slovakia
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Acute intermittent porphyria (AIP) is an autosomally dominant inherited metabolic disorders caused by decreased activity of porphobilinogen deaminase, the third enzyme in the human heme biosynthetic pathway. We report here the first mutations in the human porphobilinogen deaminase gene in seven unrelated patients from the Czech and Slovak Republics with acute intermittent porphyria. We used denaturing gradient gel electrophoresis to screen all 15 exons and exon/ intron boundaries of the porphobilinogen deaminase gene. Polymerase chain reaction products of abnormal migration patterns were subjected to direct sequencing to identify the causative mutations. Thus we revealed four novel mutations and three which have been previously described. Of the four novel mutations, two were mis-sense (G24S, V267M), one was a single base insertion (158insA) that produced a stop codon 12 codons downstream, and one was a single base substitution in intron 12 (771 + 1) resulting in a splicing defect. The three previously detected mutations were mis-sense mutations (R26C, R26H, G111R). These results suggest a high allelic heterogeneity in Czech and Slovak patients.
ISSN:0036-5513
1502-7686
DOI:10.3109/00365519709060030