Molecular Basis for Glanzmann’s Thrombasthenia (GT) in a Compound Heterozygote With Glycoprotein IIb Gene: A Proposal for the Classification of GT Based on the Biosynthetic Pathway

The genetic basis for Glanzmann’s thrombasthenia (GT) was elucidated on a compound heterozygote with glycoprotein (GP)llb gene: an opal mutation at the end of exon 17 (CGA -+ IGA) results in only a trace amount of GPllb mRNA, and a splicing mutation at the acceptor site of exon 26 (SAG + GAG) causes an in-frame, exon skipping process from exon 25 t o 27. This aberrant transcript encodes a single-chain polypeptide characterized by a 42-amino acid deletion, which includes the proteolytic cleavage site(s) and a unique, prolinerich region at the location corresponding t o the carboxylterminal of the normal GPllb archain. These characteristics are shared by a previously reported defective GPllb molecule, which is neither assembled with GPllla nor transported t o the cellular surface. Despite its normal transcription level, expression of the present defective GPllb molecule was