title: PK-LR gene mutations in pyruvate kinase deficient Portuguese patients.
abstract: In nine unrelated Portuguese patients with pyruvate kinase (PK) deficient anaemia, whose symptoms ranged from a mild chronic haemolytic anaemia to a severe 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 missense mutations or with a missense mutation and a splicing mutation had a mild haemolytic anaemia. The three patients with severe anaemia, who were transfusion dependent until splenectomy, were homozygous for the splicing site mutations IVS10(+1)G --> C or IVS8(+2)T --> G.
authors.affiliation: Unidade de Hematologia Molecular, Centro Hospitalar de Coimbra, Coimbra, Portugal.
authors.forename: L
authors.initials: L
authors.lastname: Manco
authors.forename: M L
authors.initials: ML
authors.lastname: Ribeiro
authors.forename: H
authors.initials: H
authors.lastname: Almeida
authors.forename: O
authors.initials: O
authors.lastname: Freitas
authors.forename: A
authors.initials: A
authors.lastname: Abade
authors.forename: G
authors.initials: G
authors.lastname: Tamagnini
mesh_terms: D000328:Adult; D002648:Child; D005260:Female; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D011174:Portugal; D011770:Pyruvate Kinase / Q000172:deficiency* / Q000235:genetics
chemical_list: D011770:Pyruvate Kinase