Identical point mutations of the R-type pyruvate kinase (PK) cDNA found in unrelated PK variants associated with hereditary hemolytic anemia.

PMID 1536957


We cloned and sequenced the cDNAs for R-type pyruvate kinase (R-PK) from three homozygous PK patients. A point mutation (1151ACG to ATG) identified in the R-PK cDNA of PK Nagasaki was identical with that previously identified in an unrelated family, PK Tokyo. The mutation has also been identified in the PK L gene of a Lebanese family, PK Beirut, by Neubauer et al (Blood 77:1871, 1991). These results suggest either that the point mutation is very old or that the same mutation occurs sporadically in the same hot spot in unrelated families. A point mutation, 1261CAG to AAG, was detected in both PK Fukushima and PK Maebashi; this mutation causes a single amino acid substitution, from Gln421 to Lys, in R-PK. Consequently, the hydrophobicity properties near the mutated site are drastically changed. A silent mutation (1705AGG to CGG) was also identified in those variants. The screening of these three point mutations showed only the silent mutation in a normal individual as well as in individuals with PK variants. These results indicate that the multiplicity of the mutant PK allele is smaller than expected, and that the silent mutation is a polymorphic change commonly distributed in the Japanese population.