Lerner-Ellis Jordan P, Aldubayan Saud H, Hernandez Amy Lovelette, Kelly Melissa Allard, Stuenkel Aaron J, Walsh Jennifer, Joshi Victoria A
Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada; Laboratory for Molecular Medicine, Partners Healthcare Center for Personalized Genetic Medicine, Cambridge, MA, USA.
Department of Medicine, University of Toronto, Toronto, ON, Canada.
Mol Genet Metab. 2014 Jun;112(2):171-6. doi: 10.1016/j.ymgme.2014.03.011. Epub 2014 Apr 2.
In this study, patients suspected of having a clinical diagnosis of Marfan Syndrome (MFS), Loeys-Dietz Syndrome (LDS) and Thoracic Aortic Aneurysms and Dissections (TAAD) were referred for genetic testing and examined for mutations in the FBN1, TGFβR1, TGFβR2 and ACTA2 genes.
We examined 594 samples from unrelated individuals and different combinations of genes were sequenced, including one or more of the following: FBN1, TGFβR1, TGFβR2, ACTA2, and, in some cases, FBN1 was analyzed by MLPA to detect large deletions.
A total of 112 patients had a positive result. Of those, 61 had a clinical diagnosis of MFS, eight had LDS, three had TAAD and 40 patients had clinical features with no specific diagnosis provided. A total of 44 patients had an inconclusive result; of these, 12 patients were referred with a clinical diagnosis of MFS, 4 with LDS and 9 with TAAD and 19 had no clinical diagnosis. A total of 89 mutations were novel.
This study reveals the rate of detection of variants in several genes associated with MFS, LDS and TAAD. The evaluation of patients by individuals with expertise in the field may decrease the likelihood of ordering unnecessary molecular testing. Nevertheless, genetic testing supports the diagnosis of MFS, LDS and TAAD.
在本研究中，疑似患有马凡综合征（MFS）、洛伊斯-迪茨综合征（LDS）以及胸主动脉瘤和夹层（TAAD）的患者被转诊进行基因检测，并检测其FBN1、TGFβR1、TGFβR2和ACTA2基因中的突变。
我们检测了来自无关个体的594个样本，并对不同基因组合进行测序，包括以下一种或多种：FBN1、TGFβR1、TGFβR2、ACTA2，在某些情况下，通过多重连接依赖探针扩增（MLPA）分析FBN1以检测大片段缺失。
共有112例患者检测结果为阳性。其中，61例临床诊断为MFS，8例为LDS，3例为TAAD，40例患者具有临床特征但未给出具体诊断。共有44例患者检测结果不确定；其中，12例患者临床诊断为MFS，4例为LDS，9例为TAAD，19例无临床诊断。共有89种突变是新发现的。
本研究揭示了与MFS、LDS和TAAD相关的几个基因中变异的检测率。由该领域专家对患者进行评估可能会降低进行不必要分子检测的可能性。尽管如此，基因检测支持MFS、LDS和TAAD的诊断。
