title: Acute intermittent porphyria: characterization of two novel mutations in the porphobilinogen deaminase gene, one amino acid deletion (453-455delAGC) and one splicing aceptor site mutation (IVS8-1G>T).
abstract: A partial deficiency of Porphobilinogen deaminase (PBG-D) is responsible for acute intermittent porphyria (AIP). AIP is inherited in an autosomal dominant fashion, and the prevalence in the Argentinean population is about 1:125,000. Here, two new mutations and three previously reported were found in the PBG-D gene in 12 Argentinean AIP patients corresponding to 5 different families. To screen for AIP mutations in symptomatic patients, genomic DNA isolated was amplified in 2 Multiplex PCR reactions, then all coding exons and flanking intronic regions were sequenced. The new mutations are 453-455delAGC in exon 9 which results in the loss of an alanine residue at position 152, and one new point mutation in the splicing aceptor site in the last position of intron 8 (IVS8-1G>T) which leds to a 15 bp deletion because a cryptic site (first AG upstream) is used. Both mutations produce amino acid deletion without frameshift effect. To further characterize the 453-455delAGC mutation, the pKK-PBGD construct for the mutant allele was expressed in E. coli, the enzymatic activity of the recombinant protein was 1.3% of the mean level expressed by the normal allele. Finally, three missense mutations, previously reported, were identified in three unrelated families.
authors.affiliation: Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET and Fac. Ciencias Exactas y Naturales, University of Buenos Aires, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: De Siervi
authors.forename: M
authors.initials: M
authors.lastname: Mendez
authors.forename: V E
authors.initials: VE
authors.lastname: Parera
authors.forename: L
authors.initials: L
authors.lastname: Varela
authors.forename: A M
authors.initials: AM
authors.lastname: Batlle
authors.forename: M V
authors.initials: MV
authors.lastname: Rossetti
mesh_terms: D000293:Adolescent; D000328:Adult; D004926:Escherichia coli / Q000201:enzymology; D005260:Female; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011164:Porphyrias / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D011163:Hydroxymethylbilane Synthase