More on the Association of Glucose-6-Phosphate Dehydrogenase Deficiency with Hairy-Cell Leukemia

Abstract

In a letter in the April 19, 1990, issue,¹ Egli et al. reported an interesting association between glucose-6-phosphate dehydrogenase (G6PD) deficiency and hairy-cell leukemia and suggested that a locus on the X chromosome might be involved in the latter disorder. Indeed, the genetic basis of a number of diseases in humans has been unraveled in recent years because of deletions that involved the gene of interest together with a marker gene. Examples include the linkage of the retinoblastoma gene to esterase B deficiency and the Wilms' tumor gene to a gene for aniridia. In each case the disorders occurred together because a fragment of the chromosome encompassing both adjacent genes had been deleted. However, on the basis of rapidly evolving knowledge it seemed unlikely that this would be the case with hairy-cell leukemia and G6PD deficiency. A large number of mutations causing G6PD deficiency have now been identified at the DNA level. In every case, the mutation proved to be a single nucleotide change. The absence of patients with deletions or rearrangements strongly suggests that deletions involving the G6PD gene may be lethal.