Four novel mutations in the hmbs gene responsible fo r acute intermittent porphyria

Di Pierro, D. Tavazzi, E. Bissolotti, G. Biolcati, G. Fiorelli, M. X. Cappellini

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Acute intermittent porphyria (AIP) is the most common among the acute porphyrilas and it is caused by reduced activity of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme biosynthetic pathway. Diagnosis of AIP is often difficult based pn urinary overproduction of porphyrin precursors ALA and PBG. The erythrocyte HMBS activity is not always available and informative. So far, more than 170 different mutations have been identified world-wide in the HMBS gene as responsible for AIP, showing a hi 'h genetic heterogeneity. Although AIP mutations have been identified in several ethr ic groups, little is known about HMBS molecular defects in the Italian population. In a previous work, we have identified 9 different molecular defects among 10 AIP patients y using denaturing gradient gel electrophoresis and direct sequencing. In this work we detected the molecular defect in six additional patients with typical clinical and biochemic al signs of AIP. Two of these mutations (76 CT and 612 GT) have been previously described by us and by other authors from different countries and seem to be qu te common. Four other mutations are new findings: 182 insGA, IVS9+22 GA, IVS13-1 GA and 853 CT. The molecular defects are summarized in the following table alongside to HMBS activity and biochemical data: Case n. Mutation AA subst. HMBS activity ALA(ug/24h) PBG(ug/24h) 1 76 CT R26C 47.5 11.8 18.1 2 182insGA FS/stop+37 61.9 21.3 32.1 3 IVS9+2 2OA ? 52.1 12.8 14.3 4 612 GT 9bp del in ex 10 68.0 32.5 40.8 5 IVS13-1 GA 1VS13 ins 68.4 30.4 97.9 6 853 CT T285I 58.5 7.2 3.5 CONTROLS - - 120120

Original languageEnglish
Issue number11 PART I
Publication statusPublished - 2000

ASJC Scopus subject areas

  • Hematology


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