Yao Ru-En, Wang Jian, Geng Juan, Zheng Zhaojing, Yu Tingting, Yu Yongguo, Fu Qihua
Research Division of Birth Defects, Institute of Pediatric Translational Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
J Pediatr Endocrinol Metab. 2012;25(7-8):769-73. doi: 10.1515/jpem-2012-0024.
Familial hypercholesterolemia (FH) is an autosomal dominant, inherited disease (OMIM 143890) characterized by elevated serum cholesterol bound to low-density lipoprotein (LDL). It is mainly caused by mutations of the low-density lipoprotein receptor gene (LDLR). In this study, we investigated two Chinese pedigrees with FH. The probands were a 9-year-old boy and a 1-year-old boy, who had high LDL-C levels. The proband in family A showed skin xanthoma. We sequenced the promoter and all exons and exon-intron boundaries of the LDLR gene to detect potential mutations. Compound heterozygote of c.1747C>T and c.2054C>T was detected in the proband of family A, and a heterozygous indel mutation c.551_553 delGTAinsTT was discovered in the second family. The c.1747C>T and c.2054C>T mutations, which have been reported previously, result in His583Tyr and Pro685Leu substitutions, respectively. The novel c.551_553 delGTAinsTT indel mutation causes a frameshift, which results in a p.Cys184Phe fs21X mutation in the corresponding protein.
家族性高胆固醇血症（FH）是一种常染色体显性遗传性疾病（OMIM 143890），其特征为与低密度脂蛋白（LDL）结合的血清胆固醇升高。它主要由低密度脂蛋白受体基因（LDLR）突变引起。在本研究中，我们调查了两个患有FH的中国家系。先证者分别是一名9岁男孩和一名1岁男孩，他们的低密度脂蛋白胆固醇（LDL-C）水平较高。A家族的先证者出现了皮肤黄色瘤。我们对LDLR基因的启动子、所有外显子以及外显子-内含子边界进行了测序，以检测潜在突变。在A家族的先证者中检测到c.1747C>T和c.2054C>T的复合杂合突变，在第二个家系中发现了一个杂合插入缺失突变c.551_553 delGTAinsTT。先前已报道的c.1747C>T和c.2054C>T突变分别导致His583Tyr和Pro685Leu替代。新发现的c.551_553 delGTAinsTT插入缺失突变导致移码，从而在相应蛋白质中产生p.Cys184Phe fs21X突变。
