Mutations in the β3 gene giving rise to type I Glanzmann thrombasthenia in two families in Portugal

Abstract

Glazzmann thrombasthenia is an inherited bleeding syndrome in which an absence of platelet aggregation is associated with quantitative or qualitative deficiencies of the αIIbβ3 integrin. We now describe biochemical and molecular studies on two Portuguese families where platelets lack both surface and intracellular pools of αIIbβ3. DNA extraction was followed by PCR-SSCP analysis of all exons and intronic boundaries in the αIIb and β3 genes. Migration abnormalities were found for PCR fragments encompassing exon 12 (family 1) and exon 10 (family 2). For patient 1, there was a homozygous G to T transition at position 1846 which resulted in a stop codon at codon 616 in the β3 gene. For patient 2, direct sequencing revealed a homozygous 1347C insert which led to a stop codon at codon 444 in the β3 gene. For both patients a single mutated allele was inherited from each parent. Evidence is accumulating that nonsense mutations leading to a truncated β3 may be a frequent cause of type I Glanzmann thrombasthenia in the Iberian peninsula.