Summary
We analyzed the molecular genetic defect responsible for type I Glanzmann’s thrombasthenia
in a Japanese patient. In an immunoblot assay using polyclonal anti-GPIIb-IIIa antibodies,
some GPIIIa (15% of normal amount) could be detected in the patient’s platelets, whereas
GPIIb could not (<2% of normal amount). Nucleotide sequence analysis of platelet GPIIb
mRNA-derived polymerase chain reaction (PCR) products revealed that patient’s GPIIb
cDNA had a 75-bp deletion in the 3’ boundary of exon 17 resulting in an in-frame deletion
of 25 amino acids. DNA analysis and family study revealed that the patient was a compound
heterozygote of two GPIIb gene defects. One allele derived from her father was not
expressed in platelets, and the other allele derived from her mother had a 9644C → T mutation which was located at the position -3 of the splice donor junction of
exon 17 and resulted in a termination codon (TGA). Moreover, quantitative analysis
demonstrated that the amount of the abnormal GPIIb transcript in the patient’s platelets
was markedly reduced. Thus, the C → T mutation resulting in the abnormal splicing
of GPIIb transcript and the reduction in its amount is responsible for Glanzmann’s
thrombasthenia.
