title: Study of the molecular defects in pyruvate kinase deficient patients affected by nonspherocytic hemolytic anemia.
abstract: We have examined DNA from fifteen unrelated pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia (HNSHA) for the molecular alterations responsible for the enzyme deficiency. All but 3 of the 30 putative mutations were identified. Fourteen different mutations were found. Nine were missense mutations: 320 T-->C, 823 G-->C, 1276 C-->T, 1378 G-->A, 1484 C-->T, 1529 G-->A, 1654 G-->A, 1675 C-->G; three were nonsense mutations: 603 G-->A, 721 G-->T, 1501 C-->T; one was an insertion at 1574 GGG-->GGGG and the other a three nucleotide in-frame deletion 391-392-393 ATC. Eight of these mutations have not been previously described. We also investigated all of the patients for the C/A polymorphism at nt 1705 and the microsatellite ATT repeat in intron 11. All of the mutations that had previously been reported by us (391-393del, 721T, 1484T, 1529A) were found in the context of the same haplotype as the earlier cases, supporting the concept that each may have a single origin.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: L
authors.initials: L
authors.lastname: Baronciani
authors.forename: I Q
authors.initials: IQ
authors.lastname: Magalhães
authors.forename: D H
authors.initials: DH
authors.lastname: Mahoney
authors.forename: B
authors.initials: B
authors.lastname: Westwood
authors.forename: A D
authors.initials: AD
authors.lastname: Adekile
authors.forename: T R
authors.initials: TR
authors.lastname: Lappin
authors.forename: E
authors.initials: E
authors.lastname: Beutler
mesh_terms: D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004276:DNA, Satellite / Q000235:genetics; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000172:deficiency / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004276:DNA, Satellite; D007527:Isoenzymes; D011770:Pyruvate Kinase