Pathogenic germ-line variants in GATA2 (GATA2-deficiency) can cause childhood myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), and can be associated with distinct clinical syndromic features. However, penetrance and genotype-phenotype correlations are incompletely understood. Here we report on the clinically diverse features of three siblings affected by GATA2c.1021_1031del over an 18-year period, all initially presenting in childhood and adolescence with MDS and AML with monosomy 7 (-7), and one also with trisomy 8 (+8). The siblings inherited a GATA2c.1021_1031del from their father who remains asymptomatic in his sixth decade. The two younger sisters are well after unrelated haematopoietic stem cell transplantation (HSCT), while the first boy died of severe chronic lung disease after sibling HSCT from his youngest sister, who subsequently also developed GATA2-deficiency associated MDS. This family illustrates high penetrance with variable genotype/phenotype correlation within one generation with GATA2-deficiency. We surmise that the lung disease post sibling HSCT was also caused by the GATA2-deficiency. The experience with this family underlines the necessity for GATA2 analysis in all apparently sporadic childhood and teenage MDS and AML with -7 also in the absence of a family history or other clinical features, and rigorous genetic testing in siblings. Moreover, our findings support the arguments for pre-emptive HSCT in variant-carrying siblings.

GATA2 中的致病种系变异（GATA2 缺陷）可导致儿童骨髓增生异常综合征 (MDS) 和急性髓系白血病 (AML)，并且可能与不同的临床综合征特征相关。然而，外显率和基因型-表型相关性尚不完全清楚。在这里，我们报告了在 18 年期间受GATA2c.1021_1031del影响的三个兄弟姐妹的临床多样化特征，所有兄弟姐妹都最初出现在儿童和青春期，患有 MDS 和 AML 并伴有 7 号单体 (-7)，还有一个也患有 8 三体 (+ 8). 兄弟姐妹继承了GATA2c.1021_1031del他们的父亲在他 60 岁的时候仍然没有症状。两个妹妹在无血缘关系的造血干细胞移植 (HSCT) 后恢复良好，而第一个男孩在他最小的妹妹的兄弟姐妹 HSCT 后死于严重的慢性肺病，后者随后也发生了与 GATA2 缺乏相关的 MDS。该家族说明了具有 GATA2 缺陷的一代内具有可变基因型/表型相关性的高外显率。我们推测，肺部疾病后的兄弟姐妹造血干细胞移植也引起GATA2 -不足。这个家庭的经历强调了GATA2的必要性在没有家族史或其他临床特征的情况下，对所有明显散发性的儿童和青少年 MDS 和 AML 进行分析，并在没有家族史或其他临床特征的情况下，对兄弟姐妹进行严格的基因检测。此外，我们的研究结果支持在携带变异的兄弟姐妹中进行先发制人 HSCT 的论点。