A 7 pb duplication in the PBGD caused AIP in an Argentinean family

FLAGEL MS; CERBINO G; PARERA VE; BATLLE A; ROSSETTI MV

Cardiff

Congreso; Porphyrins and Porphyrias 2011; 2011

British Association of Dermatologists

   Acute intermittent porphyria (AIP) is the most common of acutes porphyrias and it is inherited as an autosomal dominant disorder with low penetrance.  AIP is produced by a   partial deficiency in the Porphobilinogen Deaminase (PBGD) and the prevalence is approximately 1/100,000 in the Argentinean population. For a precise differential diagnosis of symptomatic patients, in same cases, and for the identification of asymptomatic carriers molecular biology techniques are used. PBGD gene spans over 10 Kb and contains 15 exons, and an alternative splicing produces two mRNAs, a ubiquitous isoform and an erythroid one. There were identified more than 300 mutations and 20 polymorphisms in the PBGD gene. However there is one mutation, a single nucleotide substitution, G111R, which is present in the 52 % of the Argentinean AIP population.    The objective of the present work is the description and characterization of a very rare new mutation in our population which is reported for the first time in the universal literature.  All exons and flanking regions were PCR amplified and automatically sequenced.    We analyzed three members of one family and we detected a 7 pb duplication in exon 7 of the PBGD, leading to a frameshift and a formation of a stop codon at 19 codons downstream in exon 8 in two sisters.  Of course both PBGD isoforms were affected.    This type of mutation identified in our country has not yet been reported and this finding supports the high heterogeneity of this porphyria.