遗传性蛋白S缺陷症一个新的基因突变

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PS1－15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55％－128％）。PS活性在13％－37％（正常值为70％－130％），较正常参考范围明确降低，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号外显子第163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PS10号外显子上第163位核苷酸发生G→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。

A novel gene mutation in a congenital protein S deficiency pedigree

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.