目的 探讨1例家族性高胆固醇血症(FH)患者LDLR基因的变异特点，为其临床诊断与遗传咨询提供依据。 方法 选取2020年6月于安徽医科大学第一附属医院生殖中心就诊的1例FH患者为研究对象。收集患者的临床资料，应用全外显子组测序(WES)对患者进行基因检测，应用Sanger测序对候选变异进行家系验证，查阅UCSC数据库进行变异位点保守性分析。 结果 患者的临床表现为血清总胆固醇水平升高，其中低密度脂蛋白胆固醇显著升高。WES结果显示患者LDLR基因存在c.2344A>T(p.Lys782*)杂合变异，既往未见报道。Sanger测序验证该变异为父源性，患者父亲LDLR基因存在c.2344A>T(p.Lys782*)杂合变异，患者母亲该位点为野生型。查询UCSC数据库提示该变异位点高度保守。 结论 LDLR基因c.2344A>T杂合变异可能为该FH患者的遗传学病因。本研究为该家系的遗传咨询和产前诊断提供了依据。 Objective To analyze variant of LDLR gene in a patient with familial hypercholesterolemia (FH) in order to provide a basis for the clinical diagnosis and genetic counseling. Methods A patient who had visited the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University in June 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was applied to the patient. Candidate variant was verified by Sanger sequencing. Conservation of the variant site was analyzed by searching the UCSC database. Results The total cholesterol level of the patient was increased, especially low density lipoprotein cholesterol. A heterozygous c. 2344A>T (p.Lys782*) variant was detected in theLDLR gene. Sanger sequencing confirmed that the variant was inherited from the father. Conclusion The heterozygous c. 2344A>T(p.Lys782*) variant of theLDLR gene probably underlay the FH in this patient. Above finding has provided a basis for genetic counseling and prenatal diagnosis for this family.
Abstract
Objective To analyze variant of LDLR gene in a patient with familial hypercholesterolemia (FH) in order to provide a basis for the clinical diagnosis and genetic counseling. Methods A patient who had visited the Reproductive Medicine Center of the First Affiliated Hospital of Anhui Medical University in June 2020 was selected as the study subject. Clinical data of the patient was collected. Whole exome sequencing (WES) was applied to the patient. Candidate variant was verified by Sanger sequencing. Conservation of the variant site was analyzed by searching the UCSC database. Results The total cholesterol level of the patient was increased, especially low density lipoprotein cholesterol. A heterozygous c. 2344A>T (p.Lys782*) variant was detected in theLDLR gene. Sanger sequencing confirmed that the variant was inherited from the father. Conclusion The heterozygous c. 2344A>T(p.Lys782*) variant of theLDLR gene probably underlay the FH in this patient. Above finding has provided a basis for genetic counseling and prenatal diagnosis for this family.
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