Artículo
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. Copyright 1999 Wiley-Liss, Inc.
Registro:
| Documento: | Artículo |
| Título: | 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). |
| Autor: | De Siervi, A.; Mendez, M.; Parera, V.E.; Varela, L.; 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: | porphobilinogen deaminase; adolescent; adult; article; biosynthesis; enzymology; Escherichia coli; female; genetics; human; male; metabolism; middle aged; mutation; porphyria; reverse transcription polymerase chain reaction; Adolescent; Adult; Escherichia coli; Female; Humans; Hydroxymethylbilane Synthase; Male; Middle Aged; Mutation; Porphyrias; Reverse Transcriptase Polymerase Chain Reaction |
| Año: | 1999 |
| Volumen: | 14 |
| Número: | 4 |
| Página de inicio: | 355 |
| DOI: | http://dx.doi.org/10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T |
| Título revista: | Human mutation |
| Título revista abreviado: | Hum. Mutat. |
| ISSN: | 10981004 |
| CAS: | porphobilinogen deaminase, 9036-47-9, 9074-91-3; Hydroxymethylbilane Synthase, EC 2.5.1.61 |
| Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10981004_v14_n4_p355_DeSiervi |
Citas:
---------- APA ----------
De Siervi, A., Mendez, M., Parera, V.E., Varela, L., Batlle, A.M. & Rossetti, M.V. (1999) . 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). Human mutation, 14(4), 355.http://dx.doi.org/10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T
---------- CHICAGO ----------
De Siervi, A., Mendez, M., Parera, V.E., Varela, L., Batlle, A.M., Rossetti, M.V. "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)." Human mutation 14, no. 4 (1999) : 355.http://dx.doi.org/10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T
---------- MLA ----------
De Siervi, A., Mendez, M., Parera, V.E., Varela, L., Batlle, A.M., Rossetti, M.V. "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)." Human mutation, vol. 14, no. 4, 1999, pp. 355.http://dx.doi.org/10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T
---------- VANCOUVER ----------
De Siervi, A., Mendez, M., Parera, V.E., Varela, L., Batlle, A.M., Rossetti, M.V. 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). Hum. Mutat. 1999;14(4):355.http://dx.doi.org/10.1002/(SICI)1098-1004(199910)14:4<355::AID-HUMU19>3.0.CO;2-T
