Department of Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands.
Clin Genet. 2013 Apr;83(4):337-44. doi: 10.1111/j.1399-0004.2012.01931.x. Epub 2012 Aug 21.
Several genes involved in the familial appearance of thoracic aortic aneurysms and dissections (FTAAD) have been characterized recently, one of which is SMAD3. Mutations of SMAD3 cause a new syndromic form of aortic aneurysms and dissections associated with skeletal abnormalities. We discovered a small interstitial deletion of chromosome 15, leading to disruption of SMAD3, in a boy with mild mental retardation, behavioral problems and revealed features of the aneurysms-osteoarthritis syndrome (AOS). Several family members carried the same deletion and showed features including aortic aneurysms and a dissection. This finding demonstrates that haploinsufficiency of SMAD3 leads to development of both thoracic aortic aneurysms and dissections, and the skeletal abnormalities that form part of the aneurysms-osteoarthritis syndrome. Interestingly, the identification of this familial deletion is an example of an unanticipated result of a genomic microarray and led to the discovery of important but unrelated serious aortic disease in the proband and family members.
最近，一些与胸主动脉瘤和夹层（FTAAD）家族性表现相关的基因已经被描述，其中之一是 SMAD3。SMAD3 的突变导致一种新的综合征形式的主动脉瘤和夹层，伴有骨骼异常。我们发现一个患有轻度智力障碍、行为问题并表现出动脉瘤-骨关节炎综合征（AOS）特征的男孩存在染色体 15 的小片段缺失，导致 SMAD3 中断。几个家族成员携带相同的缺失，并表现出包括主动脉瘤和夹层的特征。这一发现表明 SMAD3 的单倍体不足导致胸主动脉瘤和夹层的发展，以及形成动脉瘤-骨关节炎综合征一部分的骨骼异常。有趣的是，这种家族性缺失的鉴定是基因组微阵列的一个意外结果的例子，并导致在先证者和家族成员中发现了重要但不相关的严重主动脉疾病。
