Detection of Four Novel Mutations in the Porphobilinogen Deaminase Gene in French Caucasian Patients with Acute Intermittent Porphyria

• Published in: Human heredity 1996-05, Vol.46 (3), p.177-180
• Main Authors: Puy, H., Deybach, J.C., Lamoril, J., Robreau, A.M., Nordmann, Y.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Electrophoresis - methods; Errors of metabolism; European Continental Ancestry Group - genetics; France; Genes, Dominant; Humans; Hydroxymethylbilane Synthase - genetics; Medical sciences; Metabolic diseases; Mutation; Original Paper; Porphyria, Acute Intermittent - genetics; Proteins and glycoproteins
• ISSN: 0001-5652; 1423-0062
• DOI: 10.1159/000154349

Acute intermittent porphyria (AIP) is an autosomal dominant disorder characterized by alterations of the gene encoding porphobilinogen deaminase (PBGD: EC 4.3.1.8), the third enzyme of the heme biosynthetic pathway. The molecular heterogeneity of the mutations causing AIP has been demonstrated with a reported predominance of single base substitutions resulting in amino acid changes. The molecular basis of AIP in four French patients was investigated using denaturing gradient gel electrophoresis followed by direct sequencing. We describe four different novel mutations that affected exon 12 (a frameshift and an exon skipping), exon 4 (a stop codon) and exon 15 (a frameshift inducing a stop codon). This study further documents the molecular heterogeneity of mutations in the PBGD gene in the French Caucasian population and reports types of mutations relatively uncommon in AIP.