COMPOUND HETEROZYGOUS MUTATIONS AFFECTING BOTH HEPATIC AND ERYTHROCYTE ISOZYMES OF PYRUVATE-KINASE

Novel erythrocyte pyruvate kinase gene defects were found in a patient without a family history of consanguinity. The polymerase chain reaction products of the R-type pyruvate kinase cDNA from the propositus contained two point mutations of Ser(80) (TCC) --> Pro (CCC) and Arg(490) (CGG) --> Trp (TGG). Allele-specific polymerase chain reaction of the genomic DNA revealed that this patient was a compound heterozygote. The mobilities of the patient's L- and R-type pyruvate kinase by thin-layer polyacrylamide gel electrophoresis were abnormal. The results are consistent with the fact that these mutations are within exons common to the hepatic and erythrocyte isozymes. (C) 1995 Academic Press, Inc.