A 7-bp duplication in PBGD caused acute intermittent porphyria in an Argentinian family

FLAGEL, SOLEDAD; CERBINO, GABRIELA; PARERA, VICTORIA; BATLLE, ALCIRA; ROSSETTI, MARIA VICTORIA

Cardiff

Congreso; International Porphyrins and Porphyrias Meeting; 2011

Acute intermittent porphyria (AIP) is the most common of the acute porphyrias and is inherited as an autosomal dominant disorder with low penetrance. AIP is produced by a partial deficiency in porphobilinogen deaminase (PBGD) and the prevalence is approximately 1 : 100 000 in the Argentinian population. Molecular biology techniques are used for a precise differential diagnosis of symptomatic patients and for the identification of asymptomatic carriers. The PBGD gene spans over 10 kb and contains 15 exons, and an alternative splicing produces two mRNAs, a ubiquitous isoform and an erythroid one. More than 300 mutations and 20 polymorphisms have been identified in the PBGD gene. However, there is one mutation, a single nucleotide substitution, G111R, which is present in 52% of the Argentinian 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 polymerase chain reaction amplified and automatically sequenced. We analysed three members of one family and detected in two sisters a 7-bp duplication in exon 7 of PBGD, leading to a frameshift and formation of a stop codon at 19 codons downstream in exon 8. 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.