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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)
Author(s) -
De Siervi Adriana,
Mendez Manuel,
Parera Victoria Estela,
Varela Laura,
Batlle Alcira M. del C.,
Rossetti Maria Victoria
Publication year - 1999
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(199910)14:4<355::aid-humu19>3.0.co;2-t
Subject(s) - biology , frameshift mutation , porphobilinogen deaminase , genetics , exon , point mutation , microbiology and biotechnology , acute intermittent porphyria , missense mutation , porphobilinogen , mutation , gene , intron , porphyria , endocrinology
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. Hum Mutat 14:355, 1999. © 1999 Wiley‐Liss, Inc.