Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome: A 10-year single center experience
Mutation analysis of the FBN1 gene in a cohort of patients with Marfan Syndrome: A 10-year single center experience
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DOI：
10.1016/j.cca.2019.10.037
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发表时间：
2020-02-01
影响因子：
5
通讯作者：
Sangiuolo，Federica
中科院分区：
文献类型：
--
作者：
Mannucci，Liliana;Luciano，Serena;Sangiuolo，Federica
马凡氏综合征（MFS）是一种慢性、危及生命的常染色体显性结缔组织疾病，由编码纤维蛋白-1的FBN1基因突变引起。所有器官系统都可能受到影响，尤其是心血管系统、眼睛和骨骼。死亡通常由心血管并发症引起，主要是主动脉夹层。目前，MFS的诊断是基于修订的根特病分学。FBN1基因的分子分析减少了疑似MFS或MFS相关疾病（MFS- rd）患者的诊断不确定性。迄今为止，已知的FBN1突变超过2700个。方法采用下一代测序（NGS）技术，对NGS阴性样本进行多重连接依赖探针扩增，对2008年至2018年在罗马Tor Vergata医院多学科马凡诊所登记的124例无关患者（101例符合修订根特标准，20例疑似MFS， 3例MFS- rd）进行FBN1基因筛选。结果124例患者中有107例（86.3%）检出1个FBN1变异，其中新变异48个（致病/可能致病46个，VUS 2个）。在90/101 (89.1%)MFS患者中检测到致病性/可能致病性变异。我们的方法对10例疑似MFS的年轻患者（年龄3-19 岁）进行了早期诊断。结论本研究拓宽了FBN1的突变谱，为意大利MFS的分子基础提供了全面的更新。
BackgroundMarfan Syndrome (MFS) is a chronic, life-threatening, autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene, coding for fibrillin-1. All organ systems may be affected, but particularly the cardiovascular system, eyes, and skeleton. Mortality generally results from cardiovascular complications, mainly aortic dissection. Currently, the diagnosis of MFS is based on the revised Ghent nosology. Molecular analysis of the FBN1 gene reduces diagnostic uncertainty in patients with suspected MFS or MFS-related disorders (MFS-RD). To date, more than 2700 FBN1 mutations are known.MethodsUsing Next Generation Sequencing (NGS) followed by Multiplex Ligation-dependent Probe Amplification on NGS-negative samples, we screened FBN1 gene on 124 unrelated patients (101 MFS fulfilling revised Ghent criteria, 20 suspected MFS, 3 MFS-RD) enrolled from 2008 to 2018 at the Multidisciplinary Marfan Clinic, Tor Vergata Hospital, Rome.ResultsAn FBN1 variant was identified in 107/124 (86.3%) patients, including 48 novel variants (46 pathogenic/likely pathogenic, 2 VUS). A pathogenic/likely pathogenic variant was detected in 90/101 (89.1%) MFS patients. Our approach allowed early diagnosis for 10 young patients (age 3–19 years) with suspected MFS.ConclusionsThis study broadens the mutation spectrum of FBN1, providing a full update of the molecular basis of MFS in Italy.