Correlation between biochemical findings, structural and enzymatic abnormalities in mutated HMBS identified in six Israeli families with acute intermittent porphyria
| Autor: | Rivka Mamet, Vladimir Saudek, Elisabeth I. Minder, Pavel Martásek, Xiaoye Schneider-Yin, Nili Schoenfeld, Dana Ulbrichova |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male Models Molecular medicine.medical_specialty Adolescent Protein Conformation Porphobilinogen Hydroxymethylbilane Synthase DNA Mutational Analysis Mutation Missense India Biology medicine.disease_cause Structure-Activity Relationship Young Adult chemistry.chemical_compound Internal medicine medicine Humans Point Mutation Missense mutation Israel Molecular Biology Sequence Deletion Acute intermittent porphyria Aged 80 and over Mutation Protein Stability Escherichia coli Proteins Point mutation Wild type Aminolevulinic Acid Exons Cell Biology Hematology Middle Aged medicine.disease Enzyme structure Europe Endocrinology Amino Acid Substitution chemistry Jews Porphyria Acute Intermittent Molecular Medicine Female |
| Zdroj: | Blood Cells, Molecules, and Diseases. 42:167-173 |
| ISSN: | 1079-9796 |
| Popis: | Mutations in the hydroxymethylbilane synthase (HMBS) gene are responsible for the inherited disorder of acute intermittent porphyria (AIP). AIP is diagnosed on the basis of characteristic clinical symptoms, elevated levels of urinary porphyrin precursors aminolevulinic acid (ALA) and porphobilinogen (PBG) and a decreased erythrocytic HMBS activity, although an identifiable HMBS mutation provides the ultimate proof for AIP. Six Israeli AIP families underwent biochemical and mutation analysis in order to establish an AIP diagnosis. Variability with respect to the ALA/PBG levels and HBMS activity was found among the index patients. Indeed, each family carried a unique mutation in the HMBS gene. A novel missense c.95G>C (p.R32P) was shown to be a de novo mutation in one family, along with five known mutations p.T59I, p.D178N, p.V215M, c.730_731delCT and c.982_983delCA identified in the rest of the families. Both R32P and D178N were expressed in a prokaryotic system. Recombinant p.R32P was enzymatically inactive as demonstrated by a |
| Databáze: | OpenAIRE |
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