Molecular basis of glutathione reductase deficiency in human blood cells
| Autor: | Martin de Boer, Nanne Kamerbeek, Carsten Lincke, Dirk Roos, Katja Becker, Gert Morren, Rob van Zwieten, Herma Vuil, Natalja Bannink, Koert M. Dolman, Stephan Gromer, R. Heiner Schirmer |
|---|---|
| Přispěvatelé: | Landsteiner Laboratory, AII - Amsterdam institute for Infection and Immunity, Paediatric Infectious Diseases / Rheumatology / Immunology |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Heterozygote medicine.medical_specialty Erythrocytes Immunology Glutathione reductase Biology Reductase Biochemistry Cataract law.invention Blood cell chemistry.chemical_compound law Internal medicine Leukocytes medicine Humans Protein Structure Quaternary Alleles Sequence Deletion Hematology Genetic Diseases Inborn Infant Newborn Favism Heterozygote advantage Cell Biology Glutathione Middle Aged Molecular biology Jaundice Neonatal Protein Structure Tertiary Glutathione Reductase medicine.anatomical_structure Amino Acid Substitution chemistry Codon Nonsense Child Preschool Recombinant DNA Glutathione disulfide Female |
| Zdroj: | Blood, 109(8), 3560-3566. American Society of Hematology |
| ISSN: | 0006-4971 |
| Popis: | Hereditary glutathione reductase (GR) deficiency was found in only 2 cases when testing more than 15 000 blood samples. We have investigated the blood cells of 2 patients (1a and 1b) in a previously described family suffering from favism and cataract and of a novel patient (2) presenting with severe neonatal jaundice. Red blood cells and leukocytes of the patients in family 1 did not contain any GR activity, and the GR protein was undetectable by Western blotting. Owing to a 2246-bp deletion in the patients' DNA, translated GR is expected to lack almost the complete dimerization domain, which results in unstable and inactive enzyme. The red blood cells from patient 2 did not exhibit GR activity either, but the patient's leukocytes contained some residual activity that correlated with a weak protein expression. Patient 2 was found to be a compound heterozygote, with a premature stop codon on one allele and a substitution of glycine 330, a highly conserved residue in the superfamily of NAD(P)H-dependent disulfide reductases, into alanine on the other allele. Studies on recombinant GR G330A revealed a drastically impaired thermostability of the protein. This is the first identification of mutations in the GR gene causing clinical GR deficiency. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|