Deletion of leucine 61 in glucose-6-phosphate dehydrogenase leads to chronic nonspherocytic anemia, granulocyte dysfunction, and increased susceptibility to infections.
In this study the blood cells of 4 male patients from 2 unrelated families with chronic nonspherocytic anemia and recurrent bacterial infections were investigated. The activity of glucose-6- phosphate dehydrogenase (G6PD) in the red blood cells and in the granulocytes of these patients was below detection level. Moreover, their granulocytes displayed a decreased respiratory burst upon activation. Sequencing of genomic DNA revealed a novel 3-base pair (TCT) deletion in the G6PD gene, predicting the deletion of a leucine at position 61. The mutant G6PD protein was undetectable by Western blotting in the red blood cells and granulocytes of these patients. In phytohemagglutinin-stimulated lymphocytes the G6PD protein was present, but the amount of G6PD protein was strongly diminished in the patients' cells. Purified mutant protein from an Escherichia coli expression system showed decreased heat stability and decreased specific activity. Furthermore, we found that the messenger RNA of G6PD(180-182delTCT) is unstable, which may contribute to the severe G6PD deficiency observed in these patients. We propose the name "G6PD Amsterdam" for this new variant.
van Bruggen
Robin
R
Central Laboratory of the Netherlands Blood Transfusion Service (CLB), Amsterdam, The Netherlands.
Bautista
José M
JM
Petropoulou
Theoni
T
de Boer
Martin
M
van Zwieten
Rob
R
Gómez-Gallego
Felíx
F
Belohradsky
Bernd H
BH
Hartwig
Nico G
NG
Stevens
David
D
Mason
Philip J
PJ
Roos
Dirk
D
D000293:Adolescent; D000746:Anemia, Hemolytic, Congenital Nonspherocytic / Q000097:blood* / Q000150:complications / Q000235:genetics; D001424:Bacterial Infections / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D001483:Base Sequence; D002675:Child, Preschool; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000201:enzymology / Q000473:pathology; D005192:Family Health; D020022:Genetic Predisposition to Disease; D005954:Glucosephosphate Dehydrogenase / Q000097:blood / Q000235:genetics*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood / Q000150:complications* / Q000235:genetics; D006098:Granulocytes / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007930:Leucine; D008297:Male; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016897:Respiratory Burst / Q000235:genetics; D017384:Sequence Deletion
D012333:RNA, Messenger; D005954:Glucosephosphate Dehydrogenase; C464779:glucose-6-phosphate dehydrogenase Amsterdam; D007930:Leucine