A new PKLR gene mutation in the R-type promoter region affects the gene transcription causing pyruvate kinase deficiency

• Tipo: Artigo em Revista Científica Internacional
• Data: 2000

Autores

Manco, L (Autor) Outra; Ribeiro, ML (Autor) Outra; Maximo, V (Autor) Outra; Almeida, H (Autor) Outra; Costa, A (Autor) Outra; Freitas, O (Autor) Outra; Barbot, J (Autor) Outra; Abade, A (Autor) Outra; Tamagnini, G (Autor) Outra

Revista

Título: British Journal of Haematology

Vol. 110

Páginas: 993-997

ISSN: 0007-1048

Editora: Wiley-Blackwell

Indexação

ISI Web of Knowledge - 41 Citações

Scopus - 41 Citações

Outras Informações

ID Authenticus: P-000-Z17

DOI: 10.1046/j.1365-2141.2000.02283.x

Abstract (EN): Mutations in the PKLR gene responsible for pyruvate kinase (PK)-deficient anaemia are mainly located in the coding regions: 11 are in the splicing sites and, recently, three mutations have been described in the promoter region. We now report a novel point mutation A --> G on nucleotide 72, upstream from the initiation codon of the PKLR gene, in four Portuguese PK-deficient patients. This new regulatory mutation occurs within the most proximal of the four GATA motifs (GATA-A element) in the R-type promoter region. In two patients who were homozygous for this mutation, a semiquantitative reverse transcription polymerase chain reaction (PCR) procedure was used to evaluate the amount of R-PK mRNA transcript in the reticulocytes. The mRNA level was about five times lower than in normal controls, demonstrating that the PKLR gene transcription is severely affected, most probably because the -72A --> G point mutation disables the binding of the erythroid transcription factor GATA-1 to the GATA-A element. Supporting these data, the two patients homozygous for the -72A --> G mutation had severe haemolytic anaemia and were transfusion dependent until splenectomy. Two other patients who were compound heterozygous for this mutation and the previously described missense mutation 1456C --> T had a mild condition.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 5