Attanasio Monica, Pratelli Elisa, Porciani Maria Cristina, Evangelisti Lucia, Torricelli Elena, Pellicanò Giannantonio, Abbate Rosanna, Gensini Gian Franco, Pepe Guglielmina
Department of Medical and Surgical Critical Care, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
Eur J Med Genet. 2013 Jul;56(7):356-60. doi: 10.1016/j.ejmg.2013.04.006. Epub 2013 May 15.
Marfan syndrome is an autosomal dominant disorder of connective tissue caused by mutations in the gene encoding fibrillin-1 (FBN1), a matrix component of microfibrils. Dural ectasia, i.e. enlargement of the neural canal mainly located in the lower lumbar and sacral region, frequently occurs in Marfan patients. The aim of our study was to investigate the role of dural ectasia in raising the diagnosis of Marfan syndrome and its association with FBN1 mutations. We studied 40 unrelated patients suspected for MFS, who underwent magnetic resonance imaging searching for dural ectasia. In all of them FBN1 gene analysis was also performed. Thirty-seven patients resulted affected by Marfan syndrome according to the '96 Ghent criteria; in 30 of them the diagnosis was confirmed when revaluated by the recently revised criteria (2010). Thirty-six patients resulted positive for dural ectasia. The degree of dural ectasia was grade 1 in 19 patients, grade 2 in 11 patients, and grade 3 in 6 patients. In 7 (24%) patients, the presence of dural ectasia allowed to reach a positive score for systemic feature criterion. Twenty-four patients carried an FBN1 mutation, that were represented by 13 missense (54%), and 11 (46%) mutations generating a premature termination codon (PTC, frameshifts and stop codons). No mutation was detected in the remaining 16 (6 patients with MFS and 10 with related disorders according to revised Ghent criteria). The prevalence of severe (grade 2 and grade 3) involvement of dura mater was higher in patients harbouring premature termination codon (PTC) mutations than those carrying missense-mutations (8/11 vs 2/13, P = 0.0111). Our data emphasizes the importance of dural ectasia screening to reach the diagnosis of Marfan syndrome especially when it is uncertain and indicates an association between PTC mutations and severe dural ectasia in Marfan patients.
马凡综合征是一种常染色体显性结缔组织疾病，由编码原纤维蛋白-1（FBN1）的基因突变引起，FBN1是微原纤维的一种基质成分。硬脊膜扩张，即主要位于下腰椎和骶骨区域的神经管扩大，在马凡综合征患者中经常出现。我们研究的目的是调查硬脊膜扩张在提高马凡综合征诊断率中的作用及其与FBN1突变的关联。我们研究了40名疑似马凡综合征的无亲缘关系患者，他们接受了磁共振成像以寻找硬脊膜扩张。对所有患者均进行了FBN1基因分析。根据1996年根特标准，37名患者被诊断为马凡综合征；其中30名患者经最近修订的标准（2010年）重新评估后确诊。36名患者硬脊膜扩张呈阳性。19名患者的硬脊膜扩张程度为1级，11名患者为2级，6名患者为3级。在7名（24%）患者中，硬脊膜扩张的存在使全身特征标准达到阳性评分。24名患者携带FBN1突变，其中13个为错义突变（54%），11个（46%）突变为产生过早终止密码子的突变（PTC，移码突变和终止密码子）。其余16名患者（根据修订后的根特标准，6名马凡综合征患者和10名相关疾病患者）未检测到突变。携带过早终止密码子（PTC）突变的患者硬脊膜严重受累（2级和3级）的患病率高于错义突变患者（8/11比2/13，P = 0.0111）。我们的数据强调了硬脊膜扩张筛查对于马凡综合征诊断的重要性，特别是在诊断不确定时，并表明PTC突变与马凡综合征患者严重硬脊膜扩张之间存在关联。
