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Blood, 1 September 2005, Vol. 106, No. 5, pp. 1851-1856. Prepublished online as a Blood First Edition Paper on May 3, 2005; DOI 10.1182/blood-2005-02-0555. This Article Full Text (PDF) All Versions of this Article: 2005-02-0555v1 106/5/1851    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Diez, A. Articles by Bautista, J. M Search for Related Content PubMed PubMed Citation Articles by Diez, A. Articles by Bautista, J. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 17, 2005 Accepted April 18, 2005 Life threatening nonspherocytic haemolytic anaemia in a patient with a null mutation in the PKLR gene and no compensatory PKM gene expression Amalia Diez, Florinda Gilsanz, Joaquin Martinez, Susana Perez-Benavente, Nestor W Meza, and Jose M Bautista* Department of Biochemistry and Molecular Biology IV, Universidad Complutense de Madrid, Madrid, Spain Haematology Service, University Hospital 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain * Corresponding author; email: jmbau{at}vet.ucm.es. Human erythrocyte R-type pyruvate kinase (RPK) deficiency is an autosomal recessive disorder produced by mutations in the PKLR gene causing chronic nonspherocytic haemolytic anaemia. Patient survival in severe RPK deficiency has been associated with the compensatory expression in the red blood cells of M2PK, an isoenzyme showing wide tissue distribution. We describe a novel homozygous null mutation of the PKLR gene found in a female patient diagnosed before birth as having a PK deficiency. The mutant PK gene revealed an 11-nt duplication at exon 8 causing frameshift of the PKLR transcript, predicting a truncated protein inferred to have no catalytic activity. Western blot analysis and qRT-PCR detected no M2PK expression in the peripheral blood red cell fraction. The expression of mutant RPK mRNA in the red blood cells was almost six times higher than that detected in a control patient with hereditary spherocytosis. This molecular phenotypic analysis of the null mutation in the PKLR gene provides evidence for a lack of M2PK in the mature red blood cells of this patient, and suggests that normal red cell functions and survival are achieved through a population of young erythroid cells released into the circulation in response to anaemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Zanella, P. Bianchi, and E. Fermo Pyruvate kinase deficiency Haematologica, June 1, 2007; 92(6): 721 - 723. [Full Text] [PDF] R. van Wijk and W. W. van Solinge The energy-less red blood cell is lost: erythrocyte enzyme abnormalities of glycolysis Blood, December 15, 2005; 106(13): 4034 - 4042. [Abstract] [Full Text] [PDF]

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