title: Hereditary nonspherocytic hemolytic anemia caused by red cell glucose-6-phosphate isomerase (GPI) deficiency in two Portuguese patients: Clinical features and molecular study.
abstract: Glucose-6-phosphate isomerase (GPI) deficiency cause hereditary nonspherocytic hemolytic anemia (HNSHA) of variable severity in individuals homozygous or compound heterozygous for mutations in GPI gene. This work presents clinical features and genotypic results of two patients of Portuguese origin with GPI deficiency. The patients suffer from a mild hemolytic anemia (Hb levels ranging from 10 to 12.7g/mL) associated with macrocytosis, reticulocytosis, hyperbilirubinemia, hyperferritinemia and slight splenomegaly. Genomic DNA sequencing revealed in one patient homozygosity for a new missense mutation in exon 3, c.260G>C (p.Gly87Ala), and in the second patient compound heterozygosity for the same missense mutation (p.Gly87Ala), along with a frameshift mutation resulting from a single nucleotide deletion in exon 14, c.1238delA (p.Gln413Arg fs*24). Mutation p.Gln413Arg fs*24 is the first frameshift null mutation to be described in GPI deficiency. Molecular modeling suggests that the structural change induced by the p.Gly87Ala pathogenic variant has direct impact in the structural arrangement of the region close to the active site of the enzyme.
authors: Department of Hematology, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal; Research Centre for Anthropology and Health (CIAS), Department of Life Sciences, University of Coimbra, Coimbra, Portugal. Electronic address: lmanco@antrop.uc.pt.
authors: Licínio
authors: L
authors: Manco
authors: Department of Hematology, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal; Research Centre for Anthropology and Health (CIAS), Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors: Celeste
authors: C
authors: Bento
authors: Chemistry Department, University of Coimbra, Coimbra, Portugal.
authors: Bruno L
authors: BL
authors: Victor
authors: Research Centre for Anthropology and Health (CIAS), Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors: Janet
authors: J
authors: Pereira
authors: Research Centre for Anthropology and Health (CIAS), Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors: Luís
authors: L
authors: Relvas
authors: Chemistry Department, University of Coimbra, Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.
authors: Rui M
authors: RM
authors: Brito
authors: Serviço de Patologia Clínica, Hospital Infante D. Pedro, Aveiro, Portugal.
authors: Carlos
authors: C
authors: Seabra
authors: Department of Hematology, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal.
authors: Tabita M
authors: TM
authors: Maia
authors: Department of Hematology, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal; Research Centre for Anthropology and Health (CIAS), Department of Life Sciences, University of Coimbra, Coimbra, Portugal.
authors: M Letícia
authors: ML
authors: Ribeiro
mesh_terms: D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000235:genetics*; D020134:Catalytic Domain; D016368:Frameshift Mutation; D005956:Glucose-6-Phosphate Isomerase / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D011174:Portugal; D011487:Protein Conformation; D017422:Sequence Analysis, DNA
chemical_list: D005956:Glucose-6-Phosphate Isomerase
keywords: GPI deficiency; Glucose-6-phosphate isomerase (GPI); Glycolysis; Hemolytic anemia; Portugal