Five unknown mutations in the LR pyruvate kinase gene associated with severe hereditary nonspherocytic haemolytic anaemia in France

A survey of PK-deficient patients by molecular biology techniques has been performed in France in 26 unrelated families, in which at least one mutation has been characterized. The patients, of European or North African origin, exhibited approximatively 10% of PK activity. Among the PK-R mutants described, mutation G(1529) --> A (Arg-509 --> Gln) was the most frequent. The strategy followed for the description of PK mutants in France firstly involves determination of this mutation by PCR amplification and restriction enzyme digestion and, secondly, the sequencing of the gene for negative samples. Study of the mutation at residue 509 in 26 unrelated families indicated that 10/52 defective alleles possessed this mutation. Our study described seven different mutations; five of these have not as yet been documented. Two frameshift mutations were found: the deletion of one G base in a repetition of four Gs in position 1231-1234 (PK Mondor), del C-1527 (PK Rouen),and three missense mutations: G(382) --> C (Ala-114 --> Pro) (PK Val-de-Marne), C-398 --> T (Ser-119 --> Phe) (PK Beaujon), A(1217) --> G (Asn-392 --> Ser) (PK Paris). Two mutations which were detected have been reported previously: C-760 --> T (Glu-240 --> End) and G(1529) --> A (arg-509 --> Gln).