Direct sequencing of genomic DNA samples of 11 unrelated Russian AIP patients, 32 of their relatives and 50 healthy controls from northwestern Russia including Saint Petersburg revealed nine mutations in the HMBS gene.
Acute intermittent porphyria (AIP) is an inherited disorder of haem metabolism characterized by life-threatening acute neurovisceral attacks due to the induction of hepatic δ-aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency.
Molecular characterization, by digital PCR analysis of four HMBS gene mutations affecting the ubiquitous isoform of Porphobilinogen Deaminase (PBGD) in patients with Acute Intermittent Porphyria (AIP).
Our results define the extent of allelic heterogeneity and the types (41% missense; 59% truncating) and distribution (35% in exons 10, 12, 14) of HMBS mutations, for AIP in the United Kingdom.
The structure provides insights into the mechanism of action of PBGD at the molecular level and could aid the development of potential drugs for the up-regulation of PBGD activity in AIP.
A modified spectrophotometric assay for porphobilinogen deaminase: its application in the detection of both carriers and patients with acute intermittent porphyria.
Detection of a R173W mutation in the porphobilinogen deaminase gene in the Nova Scotian "foreign Protestant" population with acute intermittent porphyria: a founder effect.
Three enzymic changes have now been identified in patients with acute intermittent porphyria; a high level of delta-aminolevulinate synthase activity; a low level of uroporphyrinogen I synthase activity; and a deficiency of steroid Delta(4)-5alpha reductase activity.
Although more than 170 different mutations are known to the HMBS gene so far, over 40% of all mutations identified among the Polish AIP patients of this study are novel mutations, indicating the heterogeneity of molecular defects causing AIP.
We have studied the porphobilinogen deaminase gene transcripts from seven unrelated patients from the West of Scotland, all suffering from acute intermittent porphyria.
May 2006 update in porphobilinogen deaminase gene polymorphisms and mutations causing acute intermittent porphyria: comparison with the situation in Slavic population.
A single base insertion of C in exon 15 of the porphobilinogen deaminase (PBG-D) gene was observed in a patient with acute intermittent porphyria (AIP) by polymerase chain reaction (PCR)-direct sequencing analysis.
Previous haplotype analysis combined with genealogical data suggested a common origin of the PBGD gene mutation in the AIP families originating from northern Sweden (Lappland), where the highest prevalence of the disease (1 in 1500) is observed.
An inherited deficiency of porphobilinogen deaminase [porphobilinogen ammonia-lyase (polymerizing), EC 4.3.1.8] in humans is responsible for the autosomal dominant disease acute intermittent porphyria.