The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome.
The importance of genotype-phenotype correlation in the clinical management of Marfan syndrome.
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基因型 - 表型相关性在MARFAN综合征的临床管理中的重要性。
DOI：
10.1186/s13023-017-0754-6
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发表时间：
2018-01-22
影响因子：
3.7
通讯作者：
Cabrera-Bueno F
中科院分区：
文献类型：
--
作者：
Becerra-Muñoz VM;Gómez-Doblas JJ;Porras-Martín C;Such-Martínez M;Crespo-Leiro MG;Barriales-Villa R;de Teresa-Galván E;Jiménez-Navarro M;Cabrera-Bueno F
马凡氏综合征（MFS）是一种常染色体显性遗传疾病，其中主动脉根部扩张是发病和死亡的主要原因。在90%以上的MFS病例中发现了原纤维蛋白-1（FBN-1）基因突变。我们研究的目的是总结FBN-1的变异，并建立基因型-表型相关性，特别是在主动脉事件的发生，在一个广泛的人群中，最初的临床怀疑MFS。这项单中心前瞻性队列研究纳入了2010年9月至2016年10月期间访问遗传性主动脉病诊所的所有FBN-1基因变异患者。该研究包括90例FBN-1变异患者，对应于58个非相关家族。在发现的57个FBN-1变异体中，25个（43.9%）先前已被描述，其中23个已被鉴定为与MFS相关，而其余的是首次描述。按根特诊断标准诊断马凡氏综合征84例（93.3%）。其中44例有错义突变，其中6例发生主动脉事件（动脉瘤或夹层的预防性手术），而35例截短突变患者中有20例发生事件（13.6% vs. 57.1%，p < 0.001）。与错义突变患者相比，截短患者中这些事件倾向于发生在更早的年龄，尽管不显著（41.33 ± 3.77岁vs. 37.5 ± 9.62岁，p = 0.162）。与错义突变患者的良性病程相比，MFS和FBN-1截短变异患者的主动脉事件比例更高。因此，遗传学的发现不仅在诊断中有重要意义，而且在疑似MFS患者的危险分层和临床管理中也有重要意义。本文的在线版本（10.1186/s13023-017-0754-6）包含补充材料，可供授权用户使用。
Marfan syndrome (MFS) is a disorder of autosomal dominant inheritance, in which aortic root dilation is the main cause of morbidity and mortality. Fibrillin-1 (FBN-1) gene mutations are found in more than 90% of MFS cases. The aim of our study was to summarise variants in FBN-1 and establish the genotype-phenotype correlation, with particular interest in the onset of aortic events, in a broad population of patients with an initial clinical suspicion of MFS. This single centre prospective cohort study included all patients presenting variants in the FBN-1 gene who visited a Hereditary Aortopathy clinic between September 2010 and October 2016. The study included 90 patients with FBN-1 variants corresponding to 58 non-interrelated families. Of the 57 FBN-1 variants found, 25 (43.9%) had previously been described, 23 of which had been identified as associated with MFS, while the the remainder are described for the first time. For 84 patients (93.3%), it was possible to give a definite diagnosis of Marfan syndrome in accordance with Ghent criteria. 44 of them had missense mutations, 6 of whom had suffered an aortic event (with either prophylactic surgery for aneurysm or dissection), whereas 20 of the 35 patients with truncating mutations had suffered an event (13.6% vs. 57.1%, p < 0.001). These events tended to occur at earlier ages in patients with truncating compared to those with missense mutations, although not significantly (41.33 ± 3.77 vs. 37.5 ± 9.62 years, p = 0.162). Patients with MFS and truncating variants in FBN-1 presented a higher proportion of aortic events, compared to a more benign course in patients with missense mutations. Genetic findings could, therefore, have importance not only in the diagnosis, but also in risk stratification and clinical management of patients with suspected MFS. The online version of this article (10.1186/s13023-017-0754-6) contains supplementary material, which is available to authorized users.
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影响因子：
2.8
作者：
Gautier, Mathieu;Detaint, Delphine;Jondeau, Guillaume
通讯作者：
Jondeau, Guillaume
影响因子：
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作者：
Sakai LY;Keene DR;Renard M;De Backer J
通讯作者：
De Backer J
影响因子：
39.3
作者：
Erbel, Raimund;Aboyans, Victor;Vrints, Christiaan J. M.
通讯作者：
Vrints, Christiaan J. M.
影响因子：
5.2
作者：
Lipscomb, KJ;ClaytonSmith, J;Harris, R
通讯作者：
Harris, R
影响因子：
2.8
作者：
Devereux, Richard B.;de Simone, Giovanni;Arnett, Donna K.;Best, Lyle G.;Boerwinkle, Eric;Howard, Barbara V.;Kitzman, Lane;Lee, Elisa T.;Mosley, Thomas H., Jr.;Weder, Alan;Roman, Mary J.
通讯作者：
Roman, Mary J.