Bor M1, Balogh K2, Berkes E2, Székely E1, Pusztai Á1, Tasnádi Gy1, Hunyady L2
1Hungarian Porphyria Center, Central Hospital of the Hungarian State Railways, 2Department of Physiology, Faculty of Medicine, Semmelweis University, Budapest, Hungary
Acute intermittent porphyria (AIP) has a large allelic heterogeneity of mutations. More than 200 different mutations of the hydroxymethylbilane synthase (HMBS) gene have been identified so far. High percent of mutations are located on exon 10, 12 and 14 (1), therefore we started our work with the screening of these exons. 26 Hungarian patients from unrelated AIP families were investigated. The diagnosis of AIP was based on clinical manifestations and biochemical studies. Mutation screening was performed using temporal temperature gradient electrophoresis (TTGE) of the PCR amplified exons. Automated DNA sequencing verified the presence of the mutations in the samples with altered TTGE profile. In 12 patients eight mutations were identified. Four novel mutations were found in addition to the four previously described (R167W, R173Q, R173W, gta->ata at position 825+1) mutations. One mutation causes a splicing defect (cag->ccg at position 652-2) resulting in the skipping of exon 12. Two deletion mutations (delCGCTGAAA in exon 12 at position 744-751 and delA in exon 14 at position 911) result in a frameshift and there was one nonsense (Q292X) mutation. In conclusion, screening only 3 exons of the HMBS gene we were able to identify mutations in 46% of the Hungarian AIP patients. These data provide efficient mutation screening strategy and support the findings of other authors. Four mutations out of eight were novel. This indicates that the mutations of the Hungarian population might be quite different from the mutations of other population and also adds novel mutations to those that have been previously reported. (1) H.Puy et al: Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria. Am. J. Hum. Genet. 60: 1373-1383,1997. [This work was supported by the Hungarian Ministry of Welfare (ETT025/2000).