九例家族性高胆固醇血症患者的LDLR基因突变检测

Screening of LDLR gene mutations in nine patients with familial hypercholesterolemia

目的检测9例家族性高胆固醇血症(familial hypercholesterolemia,FH)患者的LDLR基因突变情况,为临床诊断与遗传咨询提供依据。方法PCR扩增LDLR基因的全部编码及侧翼序列,对扩增产物进行直接测序。对携带纯合突变以及复合杂合突变的患者,通过父母样本测序或T克隆测序明确突变的双等位基因来源。结果在7例患者中检出了8个LDLR基因突变,分别为c.259T>G、c.513delC、c.530C>T、c.682G>T、c.763C>T、c.1187-10G>A、c.1948delG、c.1730G>A。4例患者携带杂合突变,2例患者携带纯合突变,1例患者携带复合杂合突变,携带双等位基因突变的患者较杂合突变的患者症状更加严重。结论9例FH患者中7例检出LDLR基因突变,同时新突变位点的检出丰富了LDLR基因突变谱。

Objective To screen for LDLR gene mutations in 9 patients with familial hypercholesterolemia (FH).Methods All exons of the LDLR gene and flanking intronic sequences were amplified by PCR and subjected to automatic DNA sequencing.For patients with homozygous or compound heterozygous mutations,parental DNA sequencing or T cloning sequencing was carried out to determine the parental origin of the mutant alleles.Results Direct sequencing of PCR products revealed 8 LDLR variants in 7 patients,which included c.259T>G,c.513delC,c.530C>T,c.682G>T,c.763C>T,c.1187-10G>A,c.1948delG,and c.1730G > A,among which c.1948delG was novel.Four patients have carried heterozygous mutations, two carried homozygous mutations, and one carried compound heterozygous mutations.The patients with biallelic mutations presented with a more severe phenotype compared those carrying heterozygous mutations.Conclusion LDLR mutations were identified in 7 out of 9 patients with FH.Among the 8 identified LDLR mutations,c.1948delG was firstly reported.Above findings have expanded the mutation spectrum of LDLR gene.