Failure in the Detection of Aberrant mRNA from the Heterozygotic Splice Site Mutant Allele for Protein S in a Patient with Protein S Deficiency
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- 作者：Iida ; Hiroko ; Nakahara ; Mutsuko ; Komori ; Kimihiro ; Fujise ; Masako ; Wakiyama ; Machiko ; Urata ; Michiyo ; et. al.
- 关键词：Thrombosis ; Protein S deficiency ; Splice site mutation ; C4b binding protein ; Gene analysis ; Allelic exclusion ; PS ; protein S ; C4BP ; C4b binding protein ; APC ; activated protein C ; PC ; protein C ; AT III ; antithrombin III ; PT ; prothrombin time ; APTT ; activat
- 刊名：Thrombosis Research
- 出版年：2001
- 出版时间：May 1, 2001
- 年：2001
- 卷：102
- 期：3
- 页码：187-196
- 全文大小：424 K
文摘
A 29-year-old male patient with acute arterial obstruction and a medical history including thrombosis in the deep veins and pulmonary infarction presented with a reduced level of both protein S (PS) activity and free PS. Sequencing of the genomic PS gene in this patient revealed that the patient was heterozygous for the mutant PS allele, in which a nucleotide substitution occurred at the donor splice site in intron 12 (GT to GA). The patient was heterozygous for PS genes having dimorphic codons for Pro626 (CCA/CCG) and the aberrant allele in this patient was associated with the CCA form. Allelic exclusion of PS expression was demonstrated by use of Pro626 (CCA/CCG) dimorphism and only a normal mRNA sequence derived from the CCG-allele was identified in the patient. These findings suggested that the mutation at the splice site in the PS gene caused either defective production of mRNA or the gene may have produced extremely unstable RNA products, leading to reduced levels of PS activity and free PS in this patient.