家族性高胆固醇血症患者低密度脂蛋白受体基因新突变一例

Identification of one novel mutation of the low density lipoprotein receptor gene in Chinese patients with familial hypercholesterolemia

目的 分析中国家族性高胆固醇血症 (FH)患儿低密度脂蛋白受体 (LDL R)基因突变的情况 ,并为在婴幼儿时期此病的症前筛查提供确诊方法。方法 以患儿及其父母的基因组DNA为模板 ,首先用聚合酶链反应 (PCR)扩增该基因的启动子和全部 18个外显子 ,然后用单链构象多态性(SSCP)方法分析PCR产物 ,最后对电泳结果异常者进行DNA测序。结果 在 1个家系中检测出患儿和其父亲LDL R基因的一种新突变 ,即在第 4外显子的 44 4位碱基发生杂合突变 (T→A) ,相应的氨基酸由半胱氨酸变成终止密码子 ,其母亲LDL R基因正常。结论 LDL R基因此位点的突变可引起FH ,PCR SSCP方法可用于筛查出的高危人群的确诊。

Objective Familial hypercholesterolemia (FH) is an autosomal dominant disorder caused by mutations in the low density lipoprotein receptor (LDL-R) gene. The purpose of this study is to obtain insight into the genetic variation of LDL-R gene in Chinese patient with familial hypercholesterolemia. Methods Single strand conformation polymorphism (SSCP) analyses followed by direct sequence analysis on amplified DNA were used to find mutations in the promoter region and the 18 exons of LDL-R gening family with FH. Results One aberrant SSCP pattern was found in exon 4, and the underlying mutation was characterized by DNA sequencing. A novel missense mutation (T→A) at nucleotide site 444 was identified ,which substituted stop coden for cysteine at amino acid site of 127. Conclusions Identification of the novel mutation provides an example of the genetic heterogenerity of LDL-R causing FH.