背景：儿童骨髓增生异常肿瘤（cMDS）通常会引起对潜在种系易感性的担忧，其验证对于指导治疗选择和允许家庭咨询是必要的。这里,我们报道了一名MDS儿童的新宪法t(3;8)(p26;q21)，从父亲那里继承下来,来自母体的ANKRD26和SRP72变体，以及MDS进化过程中分子改变的获得。
方法：一名4岁女孩表现为反复感染和严重的中性粒细胞减少。骨髓表现出细胞不足，具有发育不良的特征。患者具有通过G-显带和FISH分析鉴定的t(3;8)(p26;q21)c。家族核调查确定了染色体易位的父系起源。NGS研究确定了母体来源的ANKRD26和SRP72变体。CGH阵列分析检测到PRSS3P2和KANSL基因的改变。免疫组织化学显示在MDS进化过程中p53表达异常。
结论：这项研究首次表明，遗传自父亲和母亲的细胞遗传学和基因组异常，分别,以及它们的临床意义。它还显示了调查具有结构性细胞遗传学改变和/或种系变异的患者的重要性，以向其家族细胞核提供信息，以进行遗传咨询和了解儿童MDS的发病机理。
BACKGROUND: Childhood myelodysplastic neoplasm (cMDS) often raises concerns about an underlying germline predisposition, and its verification is necessary to guide therapeutic choice and allow family counseling. Here, we report a novel constitutional t(3;8)(p26;q21) in a child with MDS, inherited from the father, the ANKRD26 and SRP72 variants from the maternal origin, and the acquisition of molecular alterations during MDS evolution.
METHODS: A 4-year-old girl showed repeated infections and severe neutropenia. Bone marrow presented hypocellularity with dysplastic features. The patient had a t(3;8)(p26;q21)c identified by G-banding and FISH analysis. The family nucleus investigation identified the paternal origin of the chromosomal translocation. The NGS study identified ANKRD26 and SRP72 variants of maternal origin. CGH-array analysis detected alterations in PRSS3P2 and KANSL genes. Immunohistochemistry showed abnormal p53 expression during the MDS evolution.
CONCLUSIONS: This study shows for the first time, cytogenetic and genomic abnormalities inherited from the father and mother, respectively, and their clinical implications. It also shows the importance of investigating patients with constitutional cytogenetic alterations and/or germline variants to provide information to their family nucleus for genetic counseling and understanding of the pathogenesis of childhood MDS.
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