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 react ion products of the R-type pyruvate kinase cDNA from the propositus co ntained two point mutations of Ser(80) (TCC) --> Pro (CCC) and Arg(490 ) (CGG) --> Trp (TGG). Allele-specific polymerase chain reaction of th e 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 ar e consistent with the fact that these mutations are within exons commo n to the hepatic and erythrocyte isozymes. (C) 1995 Academic Press, In c.