先天性血小板减少症/血小板疾病是血小板数量和/或功能的异质性疾病。在这些患者中,与巨核细胞分化和血小板形成有关的基因中的致病变异会导致血小板减少。最近的进展已经阐明了这些疾病的几个致病基因,但是识别潜在的致病基因仍然具有挑战性。患有这些疾病的患者通常会接受不适当的治疗,包括糖皮质激素和脾切除术,用于慢性免疫性血小板减少症(ITP)。在日本,我们已经开发了一种使用高通量DNA测序和多基因面板的诊断系统,并建立了一个注册表。在2018年至2023年之间,共纳入并分析了245例患者。17个基因中的致病变异(42MYH9,19ANKRD26,17ITGA2B/ITGB3,8ACTN1,8WAS,6ETV6,6VWF,5CYCS,在125例患者(51.0%)中发现了其他14例)。另有29名患者(11.8%)在调查中怀疑有致病性变异。我们还发现,未成熟的血小板分数(IPF%)在鉴别诊断中是有用的,因为在MYH9疾病中,48.7%,显著高于所有其他组(慢性ITP,13.4%;对照组,2.6%)。这项研究的结果为先天性血小板减少症/血小板疾病提供了新的见解。
Congenital thrombocytopenia/platelet disorders are heterogeneous disorders of platelet number and/or function. Pathogenic variants in the genes implicated in megakaryocyte differentiation and platelet formation cause thrombocytopenia in these patients. Recent advances have elucidated several causative genes for these disorders, but identifying the underlying causative genes remains challenging. Patients with these disorders often receive inappropriate treatments, including glucocorticoids and splenectomy, for chronic immune thrombocytopenia (ITP). In Japan, we have developed a diagnostic system using high-throughput DNA sequencing with a multigene panel and established a registry. Between 2018 and 2023, 245 patients were enrolled and analyzed. Pathogenic variants in 17 genes (42 MYH9, 19 ANKRD26, 17 ITGA2B/ITGB3, 8 ACTN1, 8 WAS, 6 ETV6, 6 VWF, 5 CYCS, and 14 others) were identified in 125 patients (51.0%). An additional 29 patients (11.8%) had suspected pathogenic variants under investigation. We also found that immature platelet fraction (IPF%) is useful in the differential diagnosis because the median IPF% in MYH9 disorders, 48.7%, was significantly higher than in all other groups (chronic ITP, 13.4%; controls, 2.6%). The results of this
study provide new insight into congenital thrombocytopenia/platelet disorders.