Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, 34480, Istanbul, Turkey.
Department of Medical Biochemistry, Faculty of Medicine, Near East University, 99138, Nicosia, Cyprus.
J Hum Genet. 2021 Jul;66(7):647-657. doi: 10.1038/s10038-021-00899-w. Epub 2021 Jan 22.
Marfan syndrome (MFS) is an autosomal dominant genetic condition that mainly affects connective tissue in many parts of the body. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. The diagnosis of MFS relies on the revised Ghent criteria, outlined by international expert opinion to facilitate accurate recognition of this syndrome as well as to improve patient management and counseling. However, it may not always be possible to make a definitive diagnosis according to these criteria in each patient and thus molecular confirmation is necessary in subjects with suspected MFS. This debilitating, if not fatal, disorder is caused by mutations in FBN1, which encodes a major constitutive element of extracellular microfibrils. Here, we present a detailed clinical and molecular analysis of 76 Turkish patients with definitive or suspected MFS diagnosed at our center between 2014 and 2019. We were able to identify a total of 51 different FBN1 variants in our cohort, 31 of which have previously been reported in the relevant scientific literature. The remaining 20 variants have not been documented to date. In one patient, we detected a large deletion including the entire FBN1 gene using the array CGH approach. Currently, there are very few studies on the genotype-phenotype correlation of patients with MFS, and no clear genotype-phenotype maps for MFS have been constructed so far, except for some cases. We believe that our findings will make a rich and peculiar contribution to the elusive genotype-phenotype relationship in MFS, especially in this large and populous ethnic group.
马凡综合征（MFS）是一种常染色体显性遗传疾病，主要影响身体多个部位的结缔组织。主要表现涉及眼部、骨骼和心血管系统。MFS 的诊断依赖于修订后的 Ghent 标准，这些标准由国际专家意见制定，旨在准确识别该综合征，改善患者管理和咨询。然而，并非每个患者都能根据这些标准做出明确的诊断，因此对于疑似 MFS 的患者，需要进行分子确认。这种使人衰弱（如果不是致命的）疾病是由编码细胞外微纤维主要组成部分的 FBN1 基因突变引起的。在这里，我们对 2014 年至 2019 年在我们中心诊断为明确或疑似 MFS 的 76 名土耳其患者进行了详细的临床和分子分析。我们在我们的队列中总共发现了 51 种不同的 FBN1 变异体，其中 31 种已经在相关科学文献中报道过。其余 20 种变异体目前尚未记录。在一名患者中，我们使用 array CGH 方法检测到包括整个 FBN1 基因在内的大片段缺失。目前，关于 MFS 患者的基因型-表型相关性的研究非常少，除了一些病例外，目前尚未构建明确的 MFS 基因型-表型图谱。我们相信，我们的发现将为 MFS 中难以捉摸的基因型-表型关系做出丰富而独特的贡献，尤其是在这个人口众多的大民族中。
