title: Two Novel Missense Mutations and a 5bp Deletion in the Erythroid-Specific Promoter of the PKLR Gene in Two Unrelated Patients With Pyruvate Kinase Deficient Transfusion-Dependent Chronic Nonspherocytic Hemolytic Anemia.
abstract: We report two children with severe chronic hemolytic anemia, the cause of which was difficult to establish because of transfusion dependency. Reduced erythrocyte pyruvate kinase activity in their asymptomatic parents provided the diagnostic clues for mutation screening of the PKLR gene and revealed that one child was a compound heterozygote of a novel paternally derived 5-bp deletion in the promoter region (c.-88_-84delTCTCT) and a maternally derived missense mutation in exon nine (c.1174G>A; p.Ala392Thr). The second child was a compound heterozygote of two novel missense mutations, namely a paternally derived exon ten c.1381G>A (p.Glu461Lys) and a maternally derived exon seven c.907-908delCC (p.Pro303GlyfsX12) variant.
authors.affiliation: St. Anna Children's Hospital, Department of Pediatrics, Medical University Vienna.|Children's Cancer Research Institute.
authors.forename: Leo
authors.initials: L
authors.lastname: Kager
authors.affiliation: St. Anna Children's Hospital, Department of Pediatrics, Medical University Vienna.|Department of Pediatrics, Hospital Rudolfstiftung.
authors.forename: Milen
authors.initials: M
authors.lastname: Minkov
authors.affiliation: medgen.at GmbH.
authors.forename: Petra
authors.initials: P
authors.lastname: Zeitlhofer
authors.affiliation: St. Anna Children's Hospital, Department of Pediatrics, Medical University Vienna.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fahrner
authors.affiliation: Department of Laboratory Medicine, Medical University Vienna.
authors.forename: Franz
authors.initials: F
authors.lastname: Ratzinger
authors.affiliation: St. Anna Children's Hospital, Department of Pediatrics, Medical University Vienna.|CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences.
authors.forename: Kaan
authors.initials: K
authors.lastname: Boztug
authors.affiliation: Department of Laboratory Medicine, Hospital Rudolfstiftung, Vienna, Austria.
authors.forename: Astrid
authors.initials: A
authors.lastname: Dossenbach-Glaninger
authors.affiliation: St. Anna Children's Hospital, Department of Pediatrics, Medical University Vienna.|Children's Cancer Research Institute.|medgen.at GmbH.
authors.forename: Oskar A
authors.initials: OA
authors.lastname: Haas
mesh_terms: D000743:Anemia, Hemolytic / Q000235:genetics / Q000628:therapy; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000235:genetics / Q000628:therapy; D001483:Base Sequence; D001803:Blood Transfusion; D002675:Child, Preschool; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000172:deficiency* / Q000235:genetics*; D015323:Pyruvate Metabolism, Inborn Errors / Q000235:genetics / Q000628:therapy; D017384:Sequence Deletion; D065227:Transfusion Reaction
chemical_list: D011770:Pyruvate Kinase
keywords: anemias; hematology nonmalignant; red blood cell disorders; transfusion