Red cell glucose phosphate isomerase (GPI): a molecular study of three novel mutations associated with hereditary nonspherocytic hemolytic anemia.
Molecular characteristics of red blood cell (RBC) glucose phosphate isomerase (GPI) deficiency are described in two Spanish patients with chronic nonspherocytic hemolytic anemia. One patient, with residual GPI activity in RBCs of around 7% (GPI-Catalonia), is homozygous for the missense mutation c.1648A>G (p.Lys550Glu) in exon 18. The other patient, with residual activity in RBCs of around 20% (GPI-Barcelona), was found to be a compound heterozygote for two different missense mutations: c.341A>T (p.Asp113Val) in exon 4 and c.663T>G (p.Asn220Lys) in exon 7. Molecular modeling using the human crystal structure of GPI as a model was performed to determine how these mutations could affect enzyme structure and function.
Repiso
Ada
A
Unitat de Bioquímica, Departament de Ciéncies Fisiològiques I, Facultat de Medicina, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain.
Oliva
Baldomero
B
Vives-Corrons
Joan-Lluis
JL
Beutler
Ernest
E
Carreras
José
J
Climent
Fernando
F
D000293:Adolescent; D000328:Adult; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000235:genetics*; D003460:Crystallization; D004252:DNA Mutational Analysis; D019281:Dimerization; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D020125:Mutation, Missense; D013329:Structure-Activity Relationship
D005956:Glucose-6-Phosphate Isomerase