Abstract：
Sitosterolemia is a rare autosomal recessive hereditary disease caused by loss-of-function genetic mutations in either ATP-binding cassette subfamily G member 5 or member 8 (ABCG5 or ABCG8). Here, we investigate novel variants in ABCG5 and ABCG8 that are associated with the sitosterolemia phenotype. We describe a 32-year-old woman with hypercholesterolemia, tendon and hip xanthomas, autoimmune hemolytic anemia and macrothrombocytopenia from early life, which make us highly suspicious of the possibility of sitosterolemia. A novel homozygous variant in ABCG5 (c.1769C>A, p.S590X) was identified by genomic sequencing. We also examined the lipid profile, especially plant sterols levels, using gas chromatography-mass spectrometry. Functional studies, including western blotting and immunofluorescence staining, showed that the nonsense mutation ABCG5 1769C>A hinders the formation of ABCG5 and ABCG8 heterodimers and the function of transporting sterols. Our study expands the knowledge of variants in sitosterolemia and provides diagnosis and treatment recommendations.
摘要：
谷甾醇血症是一种罕见的常染色体隐性遗传性疾病，由ATP结合盒亚家族G成员5或成员8（ABCG5或ABCG8）的功能丧失基因突变引起。这里,我们研究了ABCG5和ABCG8中与谷甾醇血症表型相关的新变异体.我们描述了一个32岁的女性高胆固醇血症，肌腱和髋部黄色瘤，自身免疫性溶血性贫血和早期血小板减少症，这让我们高度怀疑谷甾醇血症的可能性。ABCG5中的一种新的纯合变体（c.1769C>A，p.S590X)通过基因测序鉴定。我们还检查了脂蛋白分布，尤其是植物甾醇，通过气相色谱-质谱法检测先证者。功能研究，包括蛋白质印迹和免疫荧光染色，表明ABCG51769C>A的无义突变阻碍了ABCG5和ABCG8异二聚体的形成和运输甾醇的功能。我们的研究扩展了谷甾醇血症变异的知识，并提供了诊断和治疗建议。
