DETECTION OF 4 NOVEL MUTATIONS IN THE PORPHOBILINOGEN DEAMINASE GENE IN FRENCH CAUCASIAN PATIENTS WITH ACUTE INTERMITTENT PORPHYRIA

Acute intermittent porphyria (AIP) is an autosomal dominant disorder c haracterized by alterations of the gene encoding porphobilinogen deami nase (PBGD: EC 4.3.1.8), the third enzyme of the heme biosynthetic pat hway. The molecular heterogeneity of the mutations causing AIP has bee n demonstrated with a reported predominance of single base substitutio ns resulting in amino acid changes. The molecular basis of AIP in four French patients was investigated using denaturing gradient gel electr ophoresis followed by direct sequencing. We describe four different no vel mutations that affected exon 12 (a frameshift and an exon skipping ), exon 4 (a stop codon) and exon 15 (a frameshift inducing a stop cod on). This study further documents the molecular heterogeneity of mutat ions in the PBGD gene in the French Caucasian population and reports t ypes of mutations relatively uncommon in AIP.