[Developments of high-throughput sequencing-based diagnosis of congenital thrombocytopenia/platelet disorders in a registry study].

Akira Ishiguro, Toru Uchiyama, Atsushi Sakamoto, Shinji Kunishima
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Abstract

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.

[一项登记研究中基于高通量测序诊断先天性血小板减少症/血小板疾病的进展]。
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。巨核细胞分化和血小板形成基因中的致病变异会导致这些患者血小板减少。最近的研究进展已经阐明了这些疾病的几个致病基因,但确定潜在的致病基因仍具有挑战性。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,以治疗慢性免疫性血小板减少症(ITP)。在日本,我们利用高通量 DNA 测序技术开发了多基因面板诊断系统,并建立了登记册。2018 年至 2023 年期间,共登记并分析了 245 名患者。在 125 名患者(51.0%)中发现了 17 个基因(42 个 MYH9、19 个 ANKRD26、17 个 ITGA2B/ITGB3、8 个 ACTN1、8 个 WAS、6 个 ETV6、6 个 VWF、5 个 CYCS 和 14 个其他基因)的致病变异。另有 29 名患者(11.8%)的疑似致病变体正在调查中。我们还发现,未成熟血小板比例(IPF%)在鉴别诊断中很有用,因为 MYH9 疾病患者的 IPF% 中位数(48.7%)明显高于所有其他组别(慢性 ITP,13.4%;对照组,2.6%)。这项研究的结果为我们了解先天性血小板减少症/血小板疾病提供了新的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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