Genetic Variation of Glucose-6-Phosphate Dehydrogenase

The following review is unusual for MEDICINE. It is a survey of the mutational repertoire of the enzyme glucose-6-phosphate dehydrogenase (G6PD). As indicated by the authors, G6PD enjoys the distinction among enzymes of having the largest number of identified variant forms. Indeed, it is likely that it has the largest number of variants of any single polypeptide chain, and therefore the largest number of known mutations in 1 gene. The total number of hemoglobin variants exceeds the number of G6PD variants, but the hemoglobin variants represent the summation of changes in a number of different polypeptide chains, each coded by a different gene. G6PD, on the other hand, consists of a single polypeptide subunit, encoded by a single gene. As to definition at the gene level, i.e., description of deletions or changes in nucleotide sequence, the hemoglobins are, of course, far ahead. Indeed, relatively few G6PD variants have been characterized molecularly, even at the level of aminoacid sequence. The catalog of G6PD variants given here will provide the background for molecular studies, which are beginning in the laboratories of Drs. Beutler and Yoshida and others. The technology for such studies is now at hand, but before such studies can be undertaken the variants must be identified in the clinic. The editors of MEDICINE expect that this catalog of known variants will help in the identification of “new” ones.