Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital, Nanjing, China.
Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China; The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Suzhou, China.
Gene. 2023 Aug 30;879:147596. doi: 10.1016/j.gene.2023.147596. Epub 2023 Jun 28.
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.
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）中的功能丧失性基因突变引起。在这里，我们研究了与甾醇血症表型相关的 ABCG5 和 ABCG8 的新变体。我们描述了一位 32 岁的女性，她从早期就患有高胆固醇血症、肌腱和臀部黄色瘤、自身免疫性溶血性贫血和巨血小板减少症，这使我们高度怀疑甾醇血症的可能性。通过基因组测序鉴定出 ABCG5 中的一种新的纯合变异（c.1769C>A，p.S590X）。我们还使用气相色谱-质谱法检查了血脂谱，特别是植物甾醇水平。包括 Western blot 和免疫荧光染色在内的功能研究表明，无义突变 ABCG5 1769C>A 阻碍了 ABCG5 和 ABCG8 异二聚体的形成以及甾醇转运的功能。我们的研究扩展了甾醇血症变异的知识，并提供了诊断和治疗建议。
