PK-LR gene mutations in pyruvate kinase deficient Portuguese patients

In nine unrelated Portuguese patients with pyruvate kinase (PK) deficient a naemia, whose symptoms ranged from a mild chronic haemolytic anaemia to a s evere anaemia presenting at birth and requiring multiple transfusions, the PK-LR gene mutations were identified and correlated with their phenotypes. Five different mutations were identified. three of them for the first time: a missense mutation 1670G-->C on exon 12 and two 5' splice donor site (GT) mutations on intron 8 [IVS8(+2)T-->G] and intron 10 [IVS10(+1)G-->C]. Two previously described missense mutations, 1456C-->T and 993C-->A, were also found The genotype/phenotype correlation showed that patients with two miss ense mutations or with a missense mutation and a splicing mutation had a mi ld haemolytic anaemia. The three patients with severe anaemia, who were tra nsfusion dependent until splenectomy, were homozygous for the splicing site mutations IVS10(+1)G-->C or IVS8(+2)T-->G.