Valli R, Vinti L, Frattini A, Fabbri M, Montalbano G, Olivieri C, Minelli A, Locatelli F, Pasquali F, Maserati E
1Genetica Umana e Medica, Dipartimento di Medicina e Chirurgia, Università dell'Insubria, Varese, Italy.
2Dipartimento di Onco-Ematologia Pediatrica, Ospedale Pediatrico Bambino Gesù, Roma, Università di Pavia, Pavia, Italy.
Mol Cytogenet. 2018 Jan 11;11:2. doi: 10.1186/s13039-017-0352-2. eCollection 2018.
The majority of the cases of bone marrow failure syndromes/aplastic anaemias (BMFS/AA) are non-hereditary and considered idiopathic (80-85%). The peripheral blood picture is variable, with anaemia, neutropenia and/or thrombocytopenia, and the patients with idiopathic BMFS/AA may have a risk of transformation into a myelodysplastic syndrome (MDS) and/or an acute myeloid leukaemia (AML), as ascertained for all inherited BMFS. We already reported four patients with different forms of BMFS/AA with chromosome anomalies as primary etiologic event: the chromosome changes exerted an effect on specific genes, namely , , and , leading to the disease.
We report two further patients with non-hereditary BM failure, with diagnosis of severe aplastic anaemia and pancytopenia caused by two different constitutional structural anomalies involving chromosome 8, and possibly leading to the disorder due to effects on the gene, which was hypo-expressed and hyper-expressed, respectively, in the two patients. The chromosome change was unbalanced in one patient, and balanced in the other one.
We analyzed the sequence of events in the pathogenesis of the disease in the two patients, including a number of non-haematological signs present in the one with the unbalanced anomaly. We demonstrated that in these two patients the primary event causing BMFS/AA was the constitutional chromosome anomaly. If we take into account the cohort of 219 patients with a similar diagnosis in whom we made cytogenetic studies in the years 2003-2017, we conclude that cytogenetic investigations were instrumental to reach a diagnosis in 52 of them. We postulate that a chromosome change is the primary cause of BMFS/AA in a not negligible proportion of cases, as it was ascertained in 6 of these patients.
大多数骨髓衰竭综合征/再生障碍性贫血（BMFS/AA）病例是非遗传性的，被认为是特发性的（80 - 85%）。外周血象各异，伴有贫血、中性粒细胞减少和/或血小板减少，并且正如所有遗传性BMFS所确定的那样，特发性BMFS/AA患者可能有转化为骨髓增生异常综合征（MDS）和/或急性髓系白血病（AML）的风险。我们已经报道了4例具有不同形式BMFS/AA且染色体异常作为主要病因事件的患者：染色体变化对特定基因，即 、 和 产生影响，从而导致疾病。
我们报告另外2例非遗传性骨髓衰竭患者，诊断为严重再生障碍性贫血和全血细胞减少，由涉及8号染色体的两种不同的先天性结构异常引起，可能由于对 基因的影响导致该疾病，在这2例患者中该基因分别低表达和高表达。染色体变化在1例患者中是不平衡的，在另一例中是平衡的。
我们分析了这2例患者疾病发病机制中的一系列事件，包括在具有不平衡异常的患者中出现的一些非血液学体征。我们证明在这2例患者中，导致BMFS/AA的主要事件是先天性染色体异常。如果考虑2003 - 2017年期间我们对其进行细胞遗传学研究的219例类似诊断患者的队列，我们得出细胞遗传学检查有助于其中52例患者做出诊断。我们推测在不可忽视的一部分病例中，染色体变化是BMFS/AA的主要原因，正如在这些患者中的6例所确定的那样。
