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).

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...

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Autores principales:	De Siervi, Adriana, Mendez, Manuel, Parera, Victoria Estela, Batlle, Alcira María del Carmen, Rossetti, María Victoria
Publicado:	1999
Materias:	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 Female Humans Hydroxymethylbilane Synthase Male Middle Aged Mutation Porphyrias Reverse Transcriptase Polymerase Chain Reaction
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10981004_v14_n4_p355_DeSiervi http://hdl.handle.net/20.500.12110/paper_10981004_v14_n4_p355_DeSiervi
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_10981004_v14_n4_p355_DeSiervi
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spelling	paper:paper_10981004_v14_n4_p355_DeSiervi2023-06-08T16:07:59Z 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). De Siervi, Adriana Mendez, Manuel Parera, Victoria Estela Batlle, Alcira María del Carmen Rossetti, María Victoria 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 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. Fil:De Siervi, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Mendez, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Parera, V.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rossetti, M.V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1999 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10981004_v14_n4_p355_DeSiervi http://hdl.handle.net/20.500.12110/paper_10981004_v14_n4_p355_DeSiervi
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 De Siervi, Adriana Mendez, Manuel Parera, Victoria Estela Batlle, Alcira María del Carmen Rossetti, María Victoria 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).
topic_facet	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
description	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.
author	De Siervi, Adriana Mendez, Manuel Parera, Victoria Estela Batlle, Alcira María del Carmen Rossetti, María Victoria
author_facet	De Siervi, Adriana Mendez, Manuel Parera, Victoria Estela Batlle, Alcira María del Carmen Rossetti, María Victoria
author_sort	De Siervi, Adriana
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).
title_short	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).
title_full	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).
title_fullStr	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).
title_full_unstemmed	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).
title_sort	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).
publishDate	1999
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10981004_v14_n4_p355_DeSiervi http://hdl.handle.net/20.500.12110/paper_10981004_v14_n4_p355_DeSiervi
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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).

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