Disruption of a novel regulatory element in the erythroid-specific promoter of the human PKLR gene causes severe pyruvate kinase deficiency.

Journal article

We established the molecular basis for pyruvate kinase (PK) deficiency in a white male patient with severe nonspherocytic hemolytic anemia. The paternal allele exhibited the common PKLR cDNA sequence (c.) 1529G>A mutation, known to be associated with PK deficiency. On the maternal allele, 3 in cis mutations were identified in the erythroid-specific promoter region of the gene: one deletion of thymine -248 and 2 single nucleotide substitutions, nucleotide (nt) -324T>A and nt -83G>C. A...

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Authors: van Wijk, R; van Solinge, W; Nerlov, C; Beutler, E; Gelbart, T

• Journal: Blood
• Volume: 101
• Issue: 4
• Pages: 1596-1602
• Publication date: 2003-02-01
• DOI: 10.1182/blood-2002-07-2321
• EISSN: 1528-0020
• ISSN: 0006-4971
• Language: English
• Keywords: Molecular Sequence Data; Regulatory Sequences, Nucleic Acid; Mutagenesis, Site-Directed; Glucosephosphate Dehydrogenase; Promoter Regions, Genetic; Anemia, Hemolytic; Transfection; Male; Gene Expression; Alleles; Pyruvate Kinase; Tumor Cells, Cultured; Erythrocytes; Gene Frequency; Hexokinase; Base Sequence; Sequence Analysis, DNA; Gene Deletion; Reverse Transcriptase Polymerase Chain Reaction; Leukemia, Erythroblastic, Acute; Child; Humans; Denmark