Molecular Analyses of Pyruvate Kinase Deficient Turkish Patients from a Single Center.
Erythrocyte pyruvate kinase deficiency is one of the most common causes of hereditary non-spherocytic hemolytic anemias. We investigated molecular alterations responsible for erythrocyte pyruvate kinase enzyme deficiency in four patients of the three unrelated Turkish families available from the pool of 12 patients diagnosed as having pyruvate kinase deficiency in one center. One novel missense mutation located at cDNA nt 1623 G→C (Lys541Asn), and three previously described mutations at 1456 C→T (Arg486Trp), 1528 C→T (Arg510End), and 1675 C→G (Arg559Gly) were found to be associated with erythrocyte pyruvate kinase deficiency. All four mutations affect the C-domain of the protein. The three missense mutations result in amino acid changes, which cause an alteration in interaction between subunits by changing the local distribution of charges or by local conformational change on protein structure. The Arg510End mutation causes a deletion of terminal residues of the pyruvate kinase affecting the integrity of protein. This study presents the results of first molecular study on pyruvate kinase deficiency in Turkey.
Division of Pediatric Hematology, Department of Pediatrics, Hacettepe University , Ankara , Turkey.
Sule
S
Unal
Fatma
F
Gumruk
D019943:Amino Acid Substitution; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004795:Enzyme Stability / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011770:Pyruvate Kinase / Q000172:deficiency* / Q000235:genetics; D015323:Pyruvate Metabolism, Inborn Errors / Q000235:genetics*; D014421:Turkey
D011770:Pyruvate Kinase
C- domain; Gilbert's syndrome; hemolytic anemia; molecular study; novel mutation; pyruvate kinase