Molecular heterogeneity of glucose-6-phosphate dehydrogenase A-

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is probably the most common disease-producing genetic polymorphism of humans. Virtually all G6PD-deficient Africans show the G6PD A- phenotype, an electrophoretically rapid, deficient enzyme. The recently acquired ability to identify the point mutations producing the different variants has given us new insights into the population genetics of G6PD variants. Twenty-nine males with the G6PD A- phenotype were studied. They were of African, Mexican, Spanish, and US white ethnic origin. All had the A---G transition at nucleotide 376 characteristic of G6PD A. In each case, one of three additional mutations was present, at nucleotides 202, 680, or 968. That in this population second mutations producing G6PD deficiency occurred only on the genetic background of G6PD A suggests that G6PD A was at one time the most common type of G6PD in Africa. However, the nucleotide sequence of the chimpanzee (Pan troglodytes) G6PD indicates that the primordial human type of G6PD was G6PD B.

Molecular genetics of glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in Spain: identification of two new point mutations in the G6PD gene

“…In addition, we have found two mutations previously described in patients from other geographical areas, namely G6PD Aures (Nafa et a/, 1993) and G6PD Tomah (Hirono et al, 1989). Finally, we report two new mutations responsible for G6PD deficiency within this population, a substitution of A to G at nucleotide 209 in a molecular variant associated with favism (here referred to as G6PD Murcia), and a G to A transition at nucleotide position 1215 in a G6PD variant associated with CNSHA (previously described as G6PD Clinic) (Vives Corrons et al 1989).…”

“…One is a T + C transition at nucleotide 1153 causing the substitution of amino acid 385 from cysteine to arginine, which has been previously described in G6PD Tomah (Hirono et al 1989). The other mutation (1215 G-iA, 405 Met-iIle) has not been reported before, and is responsible for the previously described G6PD Clinic variant (Vives Corrons et al 1989). G6PD Clinic is characterized by moderate chronic haemolytic anaemia, low red cell residual G6PD activity (2.6% of normal G6PD B enzyme), and otherwise normal electrophoretic and kinetic properties.…”

“…Biochemical properties of G6PD Murcia. deficient variant characterized by a unique pH optimum found in a young patient with familial amyloid neuropathy (Vives Corrons et al, 1989). SSCP analysis of this individual revealed an abnormal mobility of a fragment containing exon 10, which by sequencing was found to be due to a G+A mutation at nucleotide position 1215.…”

Molecular characterization of G6PD deficiency in Southern Italy: heterogeneity, correlation genotype–phenotype and description of a new variant (G6PD Neapolis)

“…All samples were investigated by the PCR technique and enzyme digestion specific for the most common variants in our country, as previously reported (Calabrò et al, 1993). G6PD A variants were investigated for the presence of further mutations leading to A ¹ variants according to Beutler et al (1989). The Santamaria mutation was analysed by direct sequencing of exon VI of G6PD A samples.…”

Two new mutations of the glucose‐6‐phospate dehydrogenase (G6PD) gene associated with haemolytic anaemia: clinical, biochemical and molecular relationships

“…Genomic DNA was extracted from peripheral blood leucocytes from normal and affected individuals who were initially screened for the four mutations most frequently encountered in Spain. The DNA region from the G6PD gene encompassing each point mutation was selectively amplified by PCR using specific oligonucleotide primers as previously described (Beutler et al, 1989;Calabro et al, 1993). The naturally occurring restriction sites distinguished the normal from the mutant gene on the basis of the PCR-DNA fragments change after digestion by a particular enzyme as follows: Fok I for the 376 A→G mutation of G6PD A and G6PD A ¹ , Nla III for the 202 G→A mutation of the commonest G6PD A ¹ and 844 G→C mutation of the G6PD Seattle, Bst NI and Nci I for the 680 G→T and the 968 T→C additional mutations of the G6PD A ¹ genotypes, Mbo II for the 563 C→T mutation of G6PD Mediterranean, Hha I for the 1360 C→T mutation of G6PD Union (Rovira et al, 1994b).…”