ABSTRACT. We have examined DNA from fifteen unrelated pyruvate kinase deficient patients with hereditary nonspherocytic hemolytic anemia (HNSHA) for the molecular alterations responsible for the enzyme deficiency. All but 3 of the 30 putative mutations were identified. Fourteen different mutations were found. Nine were missense mutations: 320 T C, 823 G C, 1276 C T, 1376 C T, 1378 G A, 1484 C T, 1529 G A, 1654 G A, 1675 C G; three were nonsense mutations: 603 G A, 721 G T, 1501 C T; one was an insertion at 1574 GGG GGGG and the other a three nucleotide in-frame deletion 391-392-393 ATC. Eight of these mutations have not been previously described. We also investigated all of the patients for the C/A polymorphism at nt 1705 and the microsatellite ATT repeat in intron 11. All of the mutations that had previously been reported by us (391-393del, 721T, 1484T, 1529A) were found in the context of the same haplotype as the earlier cases, supporting the concept that each may have a single origin.

Reprint requests to:  Ernest Beutler, M.D., Department of Molecular Experimental Medicine, Scripps Research Institute, 10666 N. Torrey Pines, La Jolla, CA 92037; phone (619)554-8040, fax (619)554-6927.