Studies in porphyria. VII. Induction of uroporphyrinogen-I synthase and expression of the gene defect of acute intermittent porphyria in mitogen-stimulated human lymphocytes.
The technique described has distinct advantages over the direct enzymatic assay for URO-S activity in cultured human skin fibroblasts and permits clear differentiation of AIP carrier from normal individuals.
DNA analyses of the family members revealed that conventional assays of erythrocyte PBGD activity identified correctly only 72% of the carriers for the AIP mutation.
DNA analyses of the family members revealed that conventional assays of erythrocyte PBGD activity identified correctly only 72% of the carriers for the AIP mutation.
Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA.
The defects may be identical with those in acute intermittent porphyria (AIP), but other mechanisms are also possible, e.g. a mutation in the erythroid-specific part of the PBGD gene.
Molecular heterogeneity of acute intermittent porphyria: identification of four additional mutations resulting in the CRIM-negative subtype of the disease.
Denaturing gradient gel electrophoresis for rapid detection of latent carriers of a subtype of acute intermittent porphyria with normal erythrocyte porphobilinogen deaminase activity.
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.
Three restriction fragment length polymorphisms (RFLPs) (MspI, PstI, ScrFI/BstNI) within the human porphobilinogen deaminase (PBG-D) gene have been studied in 47 unrelated patients with the autosomal dominant disorder, acute intermittent porphyria (AIP), and in 92 control subjects.
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.
The results indicate that linkage analysis of RFLPs within the gene can be used as a complement to PBG-D analysis for the diagnosis of gene carriers in families with AIP.
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.