(G6PD and Deutan)

Several independent studies have established that the X-linked structural gene for human glucose-6-phosphate dehydrogenase (G6PD; E.C.1.1.1.49) is closely linked to the genes for both deutan and protan color blindness [1-6]. To date, only one recombinant has been directly observed between G6PD and protan out of 51 scorable sibs and five between G6PD and deutan out of 240 scorable sibs (table 1). Four of the latter were found by our group in Sardinia, and, surprisingly enough, two of them were in the same sibship [7]. This puzzling finding called for additional studies which were delayed for several years owing to the reluctance of critical family members to undergo further investigations. The pedigree has now been reexamined and expanded (fig. 1). On the basis of their phenotypes (table 2) and the derived genotype of their father (fig. 1), individuals 1I-1 and II-3 in this pedigree appear to be double heterozygotes in coupling at the loci for G6PD and deutan color-vision (d+GdBIdGdMediterranean). The two mutant phenotypes (G6PD deficiency of Mediterranean type and severe deuteranopia) or the two corresponding normal phenotypes (G6PD B type and normal color-vision) segregate together without recombination among the 12 scorable descendants of I-1. However, only one of the three G6PD deficient sons of II-3 is deuteranope, while the others have normal color-vision, suggesting the occurrence of two recombination events during maternal oogenesis. Among the alternative hypotheses to explain this finding, we considered the possibility that (1) 11-3 carries two different G6PD mutant alleles: the GdMediterranean mutant, in coupling with the gene for deuteranopic color blindness (d-) and another mutant, probably milder in its manifestation at the red cell level, associated with the