遗传性蛋白S缺陷症一个新的基因突变

A novel gene mutation in a congenital protein S deficiency pedigree

目的 研究一个遗传性蛋白S(PS)缺陷家系的遗传表型及基因型特征。方法 PS活性用凝固法测定 ,PS抗原用ELISA方法测定。用聚合酶链反应扩增 5代家系 34个成员中 9个PS活性及抗原减低的PS 1～ 15号外显子片段 ,用单链构象多态性 (SSCP)分析cDNA变性后的差异 ,用测序方法检测突变点。结果 该家系 5代 9名成员游离PS抗原在 10 %～ 45 % (正常值为 5 5 %～ 12 8% )。PS活性在 13%～ 37% (正常值为 70 %～ 130 % ) ,较正常参考范围明显降低 ,二者呈平行下降 ,但总PS抗原均在正常范围。在这些成员中均检测到 10号外显子上第 16 3位核苷酸G→T突变 ,使AGT→ATT ,在mRNA转录时 ,转录为终止密码子 ,阻断蛋白质的合成。结论 本家系的Ⅲ型PS缺陷症基因分析证明 ,先证者为杂合子型。在PS 10号外显子上第 16 3位核苷酸发生G→T突变 ,在蛋白质合成过程中丝氨酸被终止密码子替代 ,为目前文献中尚未报道的一个新的基因突变点。

Objective To study the phenotype and genotype of a protein S (PS) deficiency pedigree. Methods Detection of total and free PS antigen was carried out by ELISA, PS activity by coagulation assay, amplification of exon Ⅰ～Ⅻ fragments of PS gene by polymerase chain reaction (PCR), changes of denaturing cDNA by single strand conformation polymorphism (SSCP) and gene mutation by DNA sequencing. Results In the 9 members of the pedigree,free PS was between 10.3%～45.5%(normal range 55%～128%) and PS activity between 13%～37%( normal range 70%～130%), but total PS was normal. A G to T change in exon Ⅹ of the protein S gene was identified. This mutation resulted in a substitution of stop codon for Ser. Conclusion It was demonstrated that the proband is heterozygosity and the existance of G163 T change in exon Ⅹ of the protein S gene led to a substitution of stop codon for Ser. This mutation is a novel undescribed mutation.