title: Identification and characterization of two novel mutations that produce acute intermittent porphyria: A 3-base deletion (841-843delGGA) and a missense mutation (T35M).
abstract: A partial deficiency of Porphobilinogen deaminase (PBGD) 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 two previously reported were found in the PBGD gene in 22 Argentinean AIP patients corresponding to 8 different families. To screen for AIP mutations in symptomatic patients, genomic DNA isolated was amplified in 6 PCR reactions, then all coding exons and flanking intronic regions were sequenced. The novel mutations are 841-843delGGA in exon 14, which results in the loss of glycine-281 (G281del), and one 104C>T point mutation in the exon 4 (T35M). To further characterize both novel mutations, the pKK-PBGD construct for the mutant alleles were expressed in E. coli, the enzymatic activity of the recombinant proteins were 1% and 4% of the mean level expressed by the normal allele for 841-843delGGA and T35M, respectively. Hum Mutat 16:373, 2000.
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: D E
authors.initials: DE
authors.lastname: Weiss Cádiz
authors.forename: V E
authors.initials: VE
authors.lastname: Parera
authors.forename: A M
authors.initials: AM
authors.lastname: del C Batlle
authors.forename: M V
authors.initials: MV
authors.lastname: Rossetti
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000235:genetics*; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D017118:Porphyria, Acute Intermittent / Q000201:enzymology* / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D013912:Threonine / Q000235:genetics
chemical_list: D013912:Threonine; D008715:Methionine; D011163:Hydroxymethylbilane Synthase