Analysis of the amino acid requirement for a normal alphaIIbbeta3 maturation at alphaIIbGlu324 commonly mutated in Glanzmann thrombasthenia.

Glanzmann thrombasthenia is an inherited bleeding disorder arising from quantitative or qualitative defects of the alphaIIbbeta3 integrin of platelets. Here, we report that PCR-SSCP analysis and DNA sequencing revealed a homozygous single base pair substitution in exon 12 of the IIb gene leading to a Glu(324) (E) to Lys (K) substitution in the alphaIIb subunit in a patient with Type I disease. As this mutation is found on at least 3 continents, the codon for Glu(324) may be a mutational hotspot of the disease.

Two different beta3 cysteine substitutions alter alphaIIb beta3 maturation and result in Glanzmann thrombasthenia.

We report the defects responsible for Glanzmann thrombasthenia in two patients showing traces of abnormally migrating platelet beta3 in immunoblotting. Using PCR-SSCP and direct sequencing, we identified a novel homozygous mutation in exon 10 of the beta3 gene of patient 1 which gave a C457 to Y amino acid substitution. A C542 to R substitution in beta3 of patient 2 was previously reported by us.