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

• Type: Article in International Scientific Journal
• Date: 2000

Authors

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

Journal

Title: British Journal of Haematology

Vol. 110

Pages: 993-997

ISSN: 0007-1048

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 41 Citations

Scopus - 41 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5