Molecular basis of human carbonic anhydrase II deficiency
| Autor: | William S. Sly, Donna E. Roth, Patrick J. Venta, Richard E. Tashian |
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| Rok vydání: | 1992 |
| Předmět: |
Erythrocytes
Carbonic anhydrase II DNA Mutational Analysis Molecular Sequence Data Biology Compound heterozygosity medicine.disease_cause Polymerase Chain Reaction Renal tubular acidosis Carbonic anhydrase medicine Humans Missense mutation Cloning Molecular Carbonic Anhydrases chemistry.chemical_classification Mutation Multidisciplinary Base Sequence Osteopetrosis medicine.disease Pedigree Enzyme Oligodeoxyribonucleotides Biochemistry chemistry biology.protein Research Article |
| Zdroj: | Proceedings of the National Academy of Sciences. 89:1804-1808 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.89.5.1804 |
| Popis: | Deficiency of carbonic anhydrase II (carbonate hydro-lyase, EC 4.2.1.1) is the primary defect in the syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification. In this report we describe the molecular basis for carbonic anhydrase II deficiency in the American family in which the association of carbonic anhydrase II deficiency with this syndrome was first recognized. The three affected siblings from this family are compound heterozygotes, each having inherited two different mutations in the structural gene for carbonic anhydrase II. The paternal mutation is a splice acceptor site mutation at the 3' end of intron 5. The maternal mutation is a missense mutation in exon 3 that substitutes a tyrosine for histidine-107. We show that the mutant enzyme expressed in bacteria from the cDNA containing the His-107----Tyr mutation has detectable, though greatly reduced, activity. We suggest that residual activity of the His-107----Tyr mutant enzyme may explain the absence of mental retardation and the relatively mild phenotype of carbonic anhydrase II deficiency in affected members of this family. |
| Databáze: | OpenAIRE |
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