具有种系易感性的骨髓肿瘤（MN）已被认为是一个独特的实体。新的证据表明，散发性骨髓增生异常综合征也可能存在未被发现的种系倾向。我们调查了 122 名泰国成年 MN 患者的种系改变。招募 MN 患者并使用深度靶向下一代测序测试种系变异。使用美国医学遗传学学院分类筛选种系变异，然后评估其与临床特征和结果的关联。我们的研究结果显示 12 名患者 (10%) 存在致病性/可能致病性种系变异。这些种系损伤常见于 DNA 损伤反应途径中 (n=6, 50%)。我们还在两名诊断为再生障碍性贫血继发性急性髓系白血病 (sAML) 和与骨髓增生异常相关的 AML 的患者中发现了新的有害 FANCA A1219GfsTer59 变异。在 sAML 中，与具有野生型等位基因的个体相比，具有种系突变的个体的总生存期较差（2 个月 vs 12 个月），HR 4.7（95% CI 1.0 至 20），p=0.037。因此，致病性或可能致病性突变的存在可能与较差的生存结果有关。我们的研究强调，东南亚人群种系易感性的患病率与白种人相当。这强调了亚洲人群中种系基因检测的重要性。© 作者（或其雇主）2024。禁止商业重复使用。请参阅权利和权限。英国医学杂志出版。

Myeloid neoplasms (MNs) with germline predisposition have been recognised as a distinct entity. Emerging evidence suggests that sporadic myelodysplastic syndromes may also harbour undetected germline predispositions. We investigated germline alterations in a cohort of 122 adult Thai MNs.MN patients were recruited and tested for germline variants using deep targeted next-generation sequencing. The germline variant was filtered using American College of Medical Genetics classifications and then evaluated for the association with clinical characteristics and outcomes.Our findings revealed pathogenic/likely pathogenic germline alterations in 12 (10%) of the patients. These germline lesions were commonly found in the DNA damage response pathway (n=6, 50%). We also identified novel deleterious FANCA A1219GfsTer59 variants in two patients diagnosed with secondary acute myeloid leukaemia (sAML) from aplastic anaemia and AML with myelodysplasia related. Among sAML, individuals with germline mutations had inferior overall survival compared with those with wild-type alleles (2 months vs 12 months) with HR 4.7 (95% CI 1.0 to 20), p=0.037. Therefore, the presence of pathogenic or likely pathogenic mutations may be linked to inferior survival outcomes.Our study highlighted that the prevalence of germline predisposition in Southeast Asian populations is comparable to that in Caucasians. This underscores the importance of germline genetic testing within the Asian population.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.