家族性高胆固醇血症基因突变及临床表型研究

A genetic and clinical study in a family with familial hypercholesterolemia

目的筛查家族性高胆固醇血症家系载脂蛋白（Apo）B100基因及低密度脂蛋白受体（LDLR）基因突变，并探讨其临床表现。方法采用PCR扩增ApoBl00基因包含3500、3501、3531和3480位点的序列；扩增LDLR启动子和全部18个外显子片段，产物电泳鉴定后直接序列分析，结果与GenBank公布的基因正常序列比对，找出突变。结果该家系LDLR基因第10外显子的第1581位碱基发生G〉A突变，导致G496E突变；未检出ApoB100基因突变。结论此突变为一新突变，为该家系致病性突变。

Objective To investigate the low density lipoprotein receptor （LDLR）gene and apolipoprotein （Apo） B gene mutation in a Chinese family with familial hypercholestcrolemia（FH） and give the kindrids clinical check-ups. Methods After physical examination, the kindreds underwent ECG and ultrasound checks. Blood samples were tested for lipid profiles. The promoter and all eighteen exons of LDLR gene were investigated by using PCR and agarose gel eleetrophoresis in combination with DNA sequence analysis. The results were compared with the normal sequences in GenBank and FH database （www. ucl. ac. uk/fh ）to find mutations. In addition, the apolipoprotein B100 gene for known mutations （R3500Q,R3531C,R3501W and R3480W）that cause familial defective ApoB100 （FDB）was also tested using the same method. Results A novel homozygous G 〉 A mutation at the 1581 bp of exon 10 was detected in the proband and his siblings. It caused a substitution of amimo acid Glu to Gly at eodon 496. A novel heterozygous G 〉 A mutation at the 1581 bp of exon 10 was detected in his parents. No mutations of R3500Q, R3531 C, R3501W and R3480W of ApoB100 were observed. ECGs were normal. Atherosclerosis were found in all family members by ultrasound checks. Conclusions The homozygous G 〉 A mutation at the 1581 bp of exon 10 was first determined in our country. The change of amino acid Glu to Gly is responsible for FH of the family. The type of the gene mutation was not found in the FH database（www, ucl. ac. uk/fh）. It＇s a new type of LDLR mutation.