Fig. 1

Somatic cell mosaicism in G6PD heterozygous females and the associated G6PD activity (phenotype). X-chromosome inactivation and the phenotypic expression of G6PD deficiency in heterozygotes for GPPD mutations (a) (was Adapted from Baird et al. [61]). The top panel shows that at an early stage during embryonic development in each somatic cell of a female one of the two X chromosomes is inactivated (symbolized by a thin chromosome). In a heterozygote with one normal G6PD allele (blue) and one mutant (deficient) G6PD allele (red), after X-chromosome inactivation there are two types of cells: one type (top), where only the normal allele is expressed (blue stripe) will be G6PD normal; the other type (bottom) where only the mutant allele is expressed (red star), will be G6PD deficient. Once X inactivation has taken place it is faithfully maintained in the progeny of each cell. The bottom panel illustrates that, because X inactivation in the embryo is a random process, in adult tissue (e.g. red blood cells) the ratio between the number of cells in which one X-chromosome is inactive to the number of cells in which the other X-chromosome is active is variable: in these examples 1:9 (left), 5:5 (middle), 9:1 (right) (b) (was adapted from Bancone et al. [62]). This figure illustrates the distribution of G6PD activity in red cells from 74 G6PD heterozygous females. The G6PD activity is highly variable. The median activity is 11.76 IU/gHb so that 12 females, though heterozygous, are in the normal range, i.e. they appear to be G6PD normal (extreme phenotype). On the other hand, five females have ≲30% of the median activity, i.e. they are almost as G6PD deficient as a hemizygous male (extreme phenotype). The remaining females have intermediate G6PD levels. The dotted lines linking Fig. 1a to b show graphically how the extreme and intermediate red cell phenotypes arise