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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3560-3566. Prepublished online as a Blood First Edition Paper on December 21, 2006; DOI 10.1182/blood-2006-08-042531. This Article Full Text Full Text (PDF) Supplemental Materials and Table All Versions of this Article: blood-2006-08-042531v1 109/8/3560    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kamerbeek, N. M. Articles by Roos, D. Search for Related Content PubMed PubMed Citation Articles by Kamerbeek, N. M. Articles by Roos, D. Related Collections Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Molecular basis of glutathione reductase deficiency in human blood cells Nanne M. Kamerbeek1, Rob van Zwieten1, Martin de Boer1, Gert Morren1, Herma Vuil1, Natalja Bannink2, Carsten Lincke3, Koert M. Dolman4, Katja Becker5, R. Heiner Schirmer5, Stephan Gromer5, and Dirk Roos1 1 Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, The Netherlands; 2 Department of Pediatrics, Erasmus Medical Centre, Location Sophia, Rotterdam, The Netherlands; 3 Pediatric Department, Medical Center Rijnmond-Zuid, Location Clara, Rotterdam, The Netherlands; 4 Emma Childrens Hospital, Academic Medical Centre, University of Amsterdam, The Netherlands; 5 Biochemie-Zentrum Heidelberg, Heidelberg University, Germany 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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