家族性高胆固醇血症性黄瘤病LDL-R基因的突变

目的　研究3个家族性高胆固醇血症黄瘤病家系低密度脂蛋白受体基因突变方式，初步探讨基因型与临床表型的关系。方法　对3例先证者及25个家系成员进行血脂测定、临床检查后，采用聚合酶链反应-变性高效液相色谱，结合扩增产物直接序列分析检测低密度脂蛋白受体基因，结果与GenBank比对，分析突变的病理意义。结果　3例先证者出生时即有黄瘤，之后多处出现黄瘤，并有角膜环，可确诊为家族性高胆固醇血症黄瘤病。先证者1低密度脂蛋白受体基因发现D601N错义突变；先证者2多次出现早发冠心病症状，低密度脂蛋白受体基因发现C122Y错义突变。先证者3低密度脂蛋白受体基因未发现突变位点。28例家系成员共确诊4例杂合子患者。结论　低密度脂蛋白受体基因两个外显子的突变可能是导致家族性高胆固醇血症黄瘤病的原因。

Low-density lipoprotein-receptor gene mutations in three Chinese families with familial hypercholesterolemia and xanthomatosis

Objective To identify the low-density lipoprotein-receptor （LDL-R） gene mutations in three Chinese families with familial hypercholesterolemia and xanthomatosis, and to investigate the relationship between the genotype and phenotype of this disease. Methods Serum lipids levels were measured, and clinical examinations were performed in 3 probands and 25 family members. The LDL-R gene was assessed with PCR-denaturing high performance liquid chromatography and DNA sequencing. The sequencing results were blasted with the standard sequence of LDL-R gene in GenBank to identify the mutation sites. Results In all three probands, xanthoma was found at the buttock at birth. As they got older, more xanthomas developed at many areas of the body with corneal arcus formation, which confirmed the diagnosis of familial hypercholesterolemia and xanthomatosis. The heterozygous mutation of LDL-R gene, D601N and C122Y, was detected in proband 1 and 2, respectively. No mutation was observed in proband 3. A total of 4 heterozygous patients were confirmed in 28 family members. Conclusion The D601N and C122Y mutations of LDL-R gene may be the cause of familial hypercholesterolemia and xanthomatosis in Chinese.