title: Abnormal processing of the glycoprotein IIb transcript due to a nonsense mutation in exon 17 associated with Glanzmann's thrombasthenia.
abstract: 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.
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015252:Deoxyribonucleases, Type II Site-Specific; D005091:Exons / Q000235:genetics; D005260:Female; D005796:Genes; D006579:Heterozygote; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D013915:Thrombasthenia / Q000145:classification / Q000235:genetics*
chemical_list: D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012333:RNA, Messenger; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases