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

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked enzyme abnormality. The clinical phenotype is variable but often predictable from the molecular lesion. Class I variants (the most severe forms of the disease) 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 mutation (C269Y) of a new class I variant (G6PD Aveiro) that maps to exon 8. Mutant and normal alleles were found in both hematopoietic and buccal cells, indicating the presence of mosaicism. The available model of the protein predicts that this lesion lies in proximity to the dimer interface of the molecule. A possible mechanism to explain the severity of the defect is proposed.

Heterogeneidade Molecular da Deficiência em Glicose-6-Fosfato Desidrogenase (G6PD) na População Portuguesa

“…11 The G6PD variants Chatham (c.1003G>A), Canton (c.1376G>T) and Kamiube (c.1387C>T) were previously described in Portuguese individuals 15 and the variants Seattle (c.844G>C) and Mediterranean (c.563C>T), also found in this study, had already been previously identified in Portugal by Rodrigues et al 14 The variant G6PD Coimbra, identified in three chromosomes, was previously found in a Portuguese patient, 26 and it is common in several Asian populations. Two mutations previously described in the Portuguese population, G6PD Aveiro (c.806G>A) 27 and G6PD Gaohe (c.95A> G), 14 were not found in this study.…”

Glucose-6-phosphate dehydrogenase (G6PD) mutations and haemoglobinuria syndrome in the Vietnamese population

“…The pathogenesis of BWF remains unclear [ 14 , 15 ]. However, G6PD deficiency has been identified as a cause of haemolysis in patients receiving primaquine, or other oxidant drugs, and it is the single factor most often associated with acute intravascular haemolysis [ 3 , 4 , 8 , 16 - 18 ]. Chau et al showed in Vietnam that BWF was associated with quinine ingestion, malaria infection and G6PD deficiency, and that these three factors were not mutually independent and may interact [ 19 ].…”

Dosage Compensation in Females with X-Linked Metabolic Disorders

“…It has been noticed that there may be more than one variant of gene mutation in the population [ 177 , 178 ]. Only a few de novo mutations have been found [ 179 , 180 , 181 , 182 ]. The diagnosis of the G6PD deficiency is based on the blood count and smear (CBC), qualitative and quantitative tests of the G6PD activity, or (PCR) [ 183 , 184 , 185 , 186 ].…”