Novel type of red blood cell pyruvate kinase hyperactivity predicts a remote regulatory locus involved in PKLR gene expression. Issue 4 (3rd March 2014)

• Record Type: Journal Article
• Authors: van, Brigitte Antoinette; Francois, Jerney Johanna Jeanette Maria; van, Wouter Willem; van, Annet Cornelia Wilhelmina; Rijksen, Gert; van, Hans Kristian Ploos; van, Richard
• Is Part Of: American journal of hematology. Volume 89:Issue 4(2014:Apr.)
• Page Start: 380
• Page End: 384
• Publication Date: 2014-03-03
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.23647
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Red blood cell pyruvate kinase (PK‐R) is a key regulatory enzyme of red cell metabolism. Hereditary deficiency of PK‐R is caused by mutations in the <italic>PKLR</italic> gene, leading to chronic nonspherocytic hemolytic anemia. In contrast to PK deficiency, inherited PK hyperactivity has also been described. This very rare abnormality of RBC metabolism has been documented in only two families and appears to be without clinical consequences. Thus far, it has been attributed to either a gain of function mutation in <italic>PKLR</italic> or to persistent expression of the fetal PK isozyme PK‐M2 in mature red blood cells. We here report on a novel type of inherited PK hyperactivity that is characterized by solely increased expression of a kinetically normal PK‐R. In line with the latter, no mutations were detected in <italic>PKLR</italic>. Mutations in regulatory regions as well as variations in <italic>PKLR</italic> copy number were also absent. In addition, linkage analysis suggested that PK hyperactivity segregated independently from the <italic>PKLR</italic> locus. We therefore postulate that the causative mutation resides in a novel yet‐unidentified locus, and upregulates <italic>PKLR</italic> gene expression. Other mutations of the same locus may be involved in those cases of PK deficiency that fail to reveal mutations in <italic>PKLR</italic>. Am. J. Hematol. 89:380–384, 2014. © 2013 Wiley Periodicals, Inc.</p> </abstract>