Molecular Analysis of 29 Pyruvate Kinase–Deficient Patients From Central Europe With Hereditary Hemolytic Anemia
| Autor: | Bernd-Joachim Thiele, Claudia Lenzner, Peter Nürnberg, Christa Gerth, Gisela Jacobasch |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Hemolytic anemia
Genetics Mutation Anemia Hemolytic DNA Mutational Analysis Pyruvate Kinase Immunology DNA Cell Biology Hematology Biology medicine.disease Hereditary Hemolytic Anemia medicine.disease_cause Biochemistry Frameshift mutation Polymorphism (computer science) medicine Humans Allele Pyruvate kinase Pyruvate kinase deficiency |
| Zdroj: | Blood. 89:1793-1799 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v89.5.1793.1793_1793_1799 |
| Popis: | We investigated the DNA of 29 unrelated pyruvate kinase (PK) deficiency (PKD) patients from Central Europe with hereditary nonspherocytic hemolytic anemia for mutations in the PK-L/R gene. Among 58 potentially affected alleles, 53 mutations were identified, of which 17 were different from each other. Of these 17 mutations, 13 were single-nucleotide (nt) substitutions resulting in amino acid exchanges, G787A (Gly263-Arg), G994A (Gly332-Ser), G1006T (Ala336-Ser), G1010A (Arg337-Gln), A1081G (Asn361-Asp), G1127T (Ser376-Ile), G1174A (Ala392-Thr), G1281T (Glu427-Asp), C1454T (Ser485-Phe), C1456T (Arg486-Trp), G1493A (Arg498-His), G1529A (Arg510-Gln), and C1594T (Arg532-Trp); 1 in-frame triplet deletion, 1060delAAG (delLys354); 1 in-frame triplet insertion, 1203insAGC (insSer after Cys401); 1 splicesite mutation, 101-1G-A; and 1 frameshift deletion, 628delGT. Six mutations, 628delGT, G787A, G1010A, G1127T, G1281T, and C1454T, are described for the first time. To test the hypothesis of a single origin of the most common PK mutation in the European population, G1529A, we investigated all patients at four polymorphic sites in the PK-L/R gene: C/A at nt 1705, C/T at nt 1992, the (ATT)n microsatellite in intron J, and a polymorphism (T)10/(T)19 in intron I. Nine patients homozygous for mutation G1529A were consistent in all four markers. In the group of patients homozygous for mutation G1529A, the hematologic parameters and clinical manifestations have been studied in detail. Although having an identical mutation in the PK-L/R gene, the patients are affected differently. Their appearance ranges from a very mild compensated hemolysis to a severe anemia. Possible molecular explanations are discussed. |
| Databáze: | OpenAIRE |
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