Abstract |
Acute intermittent porphyria (AIP), an autosomal dominant disorder of heme biosynthesis, is due to mutations in hydroxymethylbilane synthase (HMBS; or porphobilinogen deaminase, PBGD) gene. In this study, we analyzed 20 Polish patients affected by AIP and we were able to characterize seven novel mutations. A nonsense mutation (Y46X), two frameshift mutations (315delT and 552delT) and a 131bp deletion (nucleotides 992-1123) give rise to truncated proteins. A donor splice site mutation IVS12+2T>C predicts skipping of exon 12. A missense mutation (D61Y) was identified in two apparently unrelated patients with a clearly clinical indication of AIP. An inframe 3-bp deletion (278-280delTTG) results in the removal of V93 from the enzyme. In addition to the novel mutations, nine previously described HMBS gene mutations-R26H, G111R, IVS7+1G>A, R149X, R173Q, 730-731delCT, R225X, 982-983delCA and G335D-were identified in this cohort. Our results demonstrate that molecular analysis of the PBGD gene is a more reliable method comparing to enzymatic assay in the diagnosis of AIP. Although more than 170 different mutations are known to the HMBS gene so far, over 40% of all mutations identified among the Polish AIP patients of this study are novel mutations, indicating the heterogeneity of molecular defects causing AIP.
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Authors | Anita Gregor, Xiaoye Schneider-Yin, Urszula Szlendak, Albert Wettstein, Agnieszka Lipniacka, Urszula B Rüfenacht, Elisabeth I Minder |
Journal | Human mutation
(Hum Mutat)
Vol. 19
Issue 3
Pg. 310
(Mar 2002)
ISSN: 1098-1004 [Electronic] United States |
PMID | 11857754
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 2002 Wiley-Liss, Inc. |
Chemical References |
- Aminolevulinic Acid
- DNA
- Hydroxymethylbilane Synthase
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Topics |
- Adult
- Aminolevulinic Acid
(urine)
- Clinical Enzyme Tests
(methods, standards)
- DNA
(genetics)
- Female
- Genetic Techniques
(standards)
- Humans
- Hydroxymethylbilane Synthase
(genetics, urine)
- Middle Aged
- Poland
- Porphyria, Acute Intermittent
(diagnosis, enzymology, genetics)
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