Red cell pyruvate kinase deficiency: 17 New mutations of the PK-LR gene

Elisa Fermo, Paola Bianchi, Laurent R. Chiarelli, Frederic Cotton, Cristina Vercellati, Karin Writzl, Kerry Baker, Ian Hann, Robin Rodwell, Giovanna Valentini, Alberto Zanella

Research output: Contribution to journalArticlepeer-review


The PK-LR gene was studied in 23 patients with congenital haemolytic anaemia associated with erythrocyte pyruvate kinase (PK) deficiency. Twenty-seven different mutations were detected among the 42 mutated alleles identified: 19 missense mutations, four splice site mutations and one nonsense, one single base deletion and two large deletions. Seventeen of them (107G, 278T, 403T, 409A, 661A, 859C, 958A, 1094T, 1190T, 1209A, 1232C, 1369G, 507A, IVS9 -1c, IVS9 +43t, del C224, del 5006bp IVS3 → nt 1431) were new. Although all the exons, the flanking regions and the promoter were sequenced in all cases, we failed to detect the second expected mutation in four subjects. To correlate genotype to phenotype, the molecular results were related to the biochemical properties of the mutant enzymes by an analysis of the three-dimensional structure of erythrocyte PK. The new mutant 409A, found in association with the large deletion of 5006 bp in a newborn baby who died soon after birth, was functionally characterized by mutagenesis and in vitro expression of the protein to investigate its contribution in the severity of the clinical pattern. However, the biochemical data obtained for the mutant enzyme cannot explain the severe anaemia found in the PK-deficient patient hemizygous for this mutation.

Original languageEnglish
Pages (from-to)839-846
Number of pages8
JournalBritish Journal of Haematology
Issue number6
Publication statusPublished - Jun 2005


  • Chronic haemolytic anaemia
  • Erythrocyte metabolism
  • Mutations
  • PK-LR gene
  • Pyruvate kinase deficiency

ASJC Scopus subject areas

  • Hematology


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