INVESTIGADORES
DE SIERVI Adriana
artículos
Título:
Identification and characterization of two novel mutations that produce Acute Intermittent Porphyria: a 3 base deletion (841-843delGGA) and a missense mutation (T35M).
Autor/es:
DE SIERVI A; WEISS CÁDIZ DE; PARERA VE; BATLLE AMC; ROSSETTI MV.
Revista:
HUMAN MUTATION
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2000 vol. 370 p. 1 - 5
ISSN:
1059-7794
Resumen:
A partial deficiency of Porphobilinogen deaminase (PBGD) is responsible for acuteintermittent porphyria (AIP). AIP is inherited in an autosomal dominant fashion, and theprevalence in the Argentinean population is about 1:125,000. Here, two new mutations andtwo previously reported were found in the PBGD gene in 22 Argentinean AIP patientscorresponding to 8 different families. To screen for AIP mutations in symptomaticpatients, genomic DNA isolated was amplified in 6 PCR reactions, then all coding exonsand flanking intronic regions were sequenced. The novel mutations are 841-843delGGA inexon 14, which results in the loss of glycine-281 (G281del), and one 104C>T point mutationin the exon 4 (T35M). To further characterize both novel mutations, the pKK-PBGDconstruct for the mutant alleles were expressed in E. coli, the enzymatic activity of therecombinant proteins were 1 % and 4 % of the mean level expressed by the normal allelefor 841-843delGGA and T35M, respectively.