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Abstract：
Myelodysplastic neoplasm (MDS) is a heterogeneous group of myeloid neoplasms affected by germline and somatic genetic alterations. The incidence of MDS increases with age but rarely occurs at a young age. We investigated the germline and somatic genetic alterations of Korean patients with young-onset MDS (<40 years). Among the thirty-one patients, five (16.1%) had causative germline variants predisposing them to myeloid neoplasms (three with GATA2 variants and one each with PGM3 and ETV variants). We found that PGM3 deficiency, a subtype of severe immunodeficiency, predisposes patients to MDS. Somatic mutations were identified in 14 patients (45.2%), with lower rates in patients aged < 20 years (11.1%). Nine (29%) patients had U2AF1 S34F/Y mutations, and patients with U2AF1 mutations showed significantly worse progression-free survival (p < 0.001) and overall survival (p = 0.006) than those without U2AF1 mutations. A UBA1 M41T mutation that causes VEXAS syndrome was identified in a male patient. In conclusion, a germline predisposition to myeloid neoplasms occurred in ~16% of young-onset MDS patients and was largely associated with primary immunodeficiencies, including GATA2 deficiency. Furthermore, the high frequency of somatic U2AF1 mutations in patients with young-onset MDS suggests the presence of a distinct MDS subtype.
摘要：
骨髓增生异常肿瘤（MDS）是一组异质性的骨髓性肿瘤，受种系和体细胞遗传改变的影响。MDS的发病率随着年龄的增长而增加，但很少发生在年轻时。我们调查了韩国年轻发病MDS患者（<40岁）的种系和体细胞遗传改变。在31名患者中，5例(16.1%)有致病性种系变异,易患髓系肿瘤(3例具有GATA2变异,1例具有PGM3和ETV变异).我们发现PGM3缺乏,严重免疫缺陷的亚型，患者易患MDS。在14例患者中发现体细胞突变（45.2％），年龄<20岁的患者发病率较低(11.1%)。9例（29%）患者有U2AF1S34F/Y突变，与没有U2AF1突变的患者相比，具有U2AF1突变的患者的无进展生存期（p<0.001）和总生存期（p=0.006）明显更差。在一名男性患者中发现了导致VEXAS综合征的UBA1M41T突变。总之,〜16％的年轻发病MDS患者发生髓系肿瘤的种系易感性，并且在很大程度上与原发性免疫缺陷有关。包括GATA2缺陷。此外，年轻起病MDS患者体内U2AF1突变的频率较高,提示存在不同的MDS亚型.
