Glucose-6-phosphate dehydrogenase Aveiro: a de novo mutation associated with chronic nonspherocytic hemolytic anemia

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked en zyme abnormality. The clinical phenotype is Variable but often predictable from the molecular lesion. Class I variants (the most severe forms of the d isease) cluster within exon 10, in a region that, at the protein level, is believed to be involved in dimerization. Here we describe a de novo mutatio n (C269Y) of a new class I Variant (G6PD Aveiro) that maps to exon 8. Mutan t and normal alleles were found in both hematopoietic and buccal cells, ind icating the presence of mosaicism. The available model of the protein predi cts that this lesion lies in proximity to the dimer interface of the molecu le. A possible mechanism to explain the severity of the defect is proposed. (C) 2000 by The American Society of Hematology.