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. Copyright 2000 Wiley-Liss, Inc.
| Documento: | Artículo |
| 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: | De Siervi, A.; Weiss Cádiz, D.E.; Parera, V.E.; del C Batlle, A.M.; Rossetti, M.V. |
| Filiación: | Centro de Investigaciones sobre Porfirinas y Porfirias, CONICET and Fac. Ciencias Exactas y Naturales, University of Buenos Aires, Argentina |
| Palabras clave: | methionine; porphobilinogen deaminase; threonine; acute intermittent porphyria; adolescent; adult; article; child; enzymology; female; gene deletion; genetics; human; male; middle aged; missense mutation; Adolescent; Adult; Child; Female; Humans; Hydroxymethylbilane Synthase; Male; Methionine; Middle Aged; Mutation, Missense; Porphyria, Acute Intermittent; Sequence Deletion; Threonine |
| Año: | 2000 |
| Volumen: | 16 |
| Número: | 4 |
| Página de inicio: | 373 |
| Título revista: | Human mutation |
| Título revista abreviado: | Hum. Mutat. |
| ISSN: | 10981004 |
| CAS: | methionine, 59-51-8, 63-68-3, 7005-18-7; porphobilinogen deaminase, 9036-47-9, 9074-91-3; threonine, 36676-50-3, 72-19-5; Hydroxymethylbilane Synthase, EC 2.5.1.61; Methionine, 63-68-3, 72-19-5; Threonine, 72-19-5 |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10981004_v16_n4_p373_DeSiervi |
