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。