Rare Co-occurrence of Beta-Thalassemia and Pseudoxanthoma elasticum: Novel Biomolecular Findings
Rare Co-occurrence of Beta-Thalassemia and Pseudoxanthoma elasticum: Novel Biomolecular Findings
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DOI：
10.3389/fmed.2019.00322
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发表时间：
2020-01-23
影响因子：
3.9
通讯作者：
Quaglino, Daniela
中科院分区：
文献类型：
--
作者：
Boraldi, Federica;Lofaro, Francesco Demetrio;Quaglino, Daniela
许多β-地中海贫血患者与β-地中海贫血类型(β(0)或β(+))和输血要求无关，在青春期后可能会出现皮肤、心血管和眼部并发症，并与另一种罕见的遗传性疾病--弹性假黄瘤(PXE)中观察到的异位矿化表型相似。到目前为止，β-地中海贫血患者这些改变的原因尚不清楚，但已有研究表明，这些改变可能是氧化应激驱动的表观遗传调节机制产生ABCC6下调的结果。由于在过去的几年中，有几个基因与异位矿化表型有关，本研究首次将多基因检测策略应用于具有异位矿化表型的β-地中海贫血患者。要分析的基因的选择是基于(I)它们在钙化疾病中的遗传参与或(Ii)它们在钙-磷平衡中的作用。尽管由于这些疾病的罕见，对有限数量的患者进行了分析，但致病变异的检测代表了PXE和β-地中海贫血特征在遗传基础上共存的概念证明，除了致病突变外，功能多态可能进一步影响结缔组织的表现。基于多基因的下一代测序的使用代表了一种有用的时间和成本效益的方法，允许识别可能改善预后评估和对这些患者的更好管理的序列变异，特别是在当前的精准医学时代，旨在根据独特的个人资料识别个人最佳护理。
A number of beta-thalassemia patients, independently from the type of beta-thalassemia (beta(0) or beta(+)) and blood transfusion requirements, may develop, after puberty, dermal, cardiovascular, and ocular complications associated with an ectopic mineralization phenotype similar to that observed in another rare genetic disorder, namely, Pseudoxanthoma elasticum (PXE). To date, the causes of these alterations in beta-thalassemia patients are not known, but it has been suggested that they could be the consequence of oxidative stress-driven epigenetic regulatory mechanisms producing an ABCC6 down-regulation. Since, in the last years, several genes have been associated to the ectopic mineralization phenotype, this study, for the first time, applied, on beta-thalassemia patients with ectopic mineralization phenotype, a multigene testing strategy. Selection of genes to be analyzed was done on the basis of (i) their genetic involvement in calcification diseases or (ii) their role in calcium-phosphate equilibrium. Although, due to the rarity of these conditions, a limited number of patients was analyzed, the detection of pathogenic variants represents the proof of concept that PXE and beta-thalassemia traits co-occur on a genetic basis and that, in addition to causative mutations, functional polymorphisms may further influence connective tissue manifestations. The use of a multigene-based next-generation sequencing represents a useful time- and cost-effective approach, allowing to identify sequence variants that might improve prognostic assessment and better management of these patients, especially in the current era of precision medicine aiming to identify individual optimal care based on a unique personal profile.