New Mutations of Porphobilinogen Deaminase Gene in Polish Families with Acute Intermittent Porphyria

Background. Acute intermittent porphyria (AIP) is an autosomal dominantly inherited disorder of low clinical penetrance. A 50% lower activity of porphobilinogen deaminase (PBGD) stands for the metabolic error in AIP. The PBGD gene is composed of 15 exons of 39-438 bp in length and it is mapped to 11q24.1-24.2 chromosome. So far over 300 various mutations of the PBGD gene responsible for AIP have been described. Objectives. Description of molecular background of AIP in patients from Polish population diagnosed based on biochemical analyses. Molecular diagnosis of AIP in family members. Material and Methods. Biochemical study, such as porphobilinogen (PBG) and delta-aminolevulinic acid (ALA) excretion with urine and PBGD activity in erythrocyres have been examined in all probands and family members. AIP patients and their family members underwent further molecular diagnosis. Results. Among 16 families with AIP diagnosis made on biochemical tests 10 new PBGD gene mutations have been discovered not yet described. Missense (83G>T, 89T>G, 281T>G, 293A>C, 500G>C and 796G>C); and frameshift (470delT, 716-725delACGATCCCGA, 723-724insCC and 969delT) mutation types have been revealed. Conclusions. Similar to other populations, 10 new mutations revealed in Polish population can suggest heterogeneity of mutatios responsible for AIP. Biochemical methods can sometimes fail to diagnose the disease. Molecular analysis is much more reliable method to diagnose AIP in asymptomatic members of probands (Adv Clin Exp Med 2010, 19, 4, 497-501).