Aortic aneurysms - An immune disease with a strong genetic component
Aortic aneurysms - An immune disease with a strong genetic component
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DOI：
10.1161/circulationaha.107.690982
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发表时间：
2008-01-15
期刊：
影响因子：
37.8
通讯作者：
Tilson, M. David, III
中科院分区：
文献类型：
--
作者：
Kuivaniemi, Helena;Platsoucas, Chris D.;Tilson, M. David, III
指出患者不符合马凡综合征的诊断标准。此后发表了许多报告，系统研究已证实20%的非综合征型TAAD患者有动脉瘤阳性家族史。 12 大多数 TAAD 家族似乎符合常染色体显性遗传模式。迄今为止，通过基于家族的方法在 DNA 连锁研究中已鉴定出 5 个 TAAD 易感位点，通过候选基因方法发现了 13 个和第 6 个位点。 14 这些位点被指定为 AAT1 至 AAT6（表 1），包括 3p24–25、13 5q13–14、13 9q33–q34、14 11q23–24、15q24–26、13 和 16p13。 13–p13。 12. 15 其中两个基因座（3p24-25 和 9q33-q34）与 Loeys-Dietz 综合征的遗传位点完全相同，Loeys-Dietz 综合征是一种罕见的常染色体显性遗传疾病，其特征为距离过长、颅缝早闭、脑结构异常、智力低下、先天性心脏病、伴有或不伴有腭裂的悬雍垂裂以及伴有上升的全身动脉迂曲主动脉瘤和夹层。此外，该家族还用于鉴定16p13上的AAT4位点。 13–p13。 12 是一个有 178 名成员的法国大家庭，患有 TAAD 和动脉导管未闭。这些发现表明，综合征型和非综合征型 TAAD 在分子水平上存在一些重叠。从目前鉴定出的6个TAAD位点来看，TAAD的遗传异质性已经很明显。然而，他们并没有解释所有已研究家族中 TAAD 的家族聚集，这表明还会发现其他基因座。 13
noted that the patients did not fit the diagnostic criteria of Marfan syndrome. Many reports have been published since then, and systematic studies have established that 20% of nonsyndromic TAAD patients have a positive family history for aneurysms. 12 Most TAAD families appear to be consistent with the autosomal dominant inheritance pattern. To date, 5 susceptibility loci for TAAD have been identified in DNA linkage studies with family-based approaches, 13 and a sixth locus was found by the candidate gene approach. 14 The loci have been designated as AAT1 through AAT6 (Table 1) and include 3p24–25, 13 5q13–14, 13 9q33–q34, 14 11q23–24, 15q24–26, 13 and 16p13. 13–p13. 12. 15 Two of the loci (3p24–25 and 9q33–q34) are exactly the same as the genetic loci for Loeys-Dietz syndrome, a rare autosomal dominant disease characterized by hypertelorism, craniosynostosis, structural brain abnormalities, mental retardation, congenital heart disease, bifid uvula with or without cleft palate, and generalized arterial tortuosity with ascending aortic aneurysm and dissection. In addition, the family used for the identification of the AAT4 locus on 16p13. 13–p13. 12 was a large 178-member French family with TAAD and patent ductus arteriosus. These findings suggest that there is some overlap between the syndromic and nonsyndromic forms of TAAD on the molecular level. On the basis of the 6 TAAD loci identified thus far, genetic heterogeneity of TAAD is already obvious. However, they do not explain the familial aggregation of TAAD in all the families that have been studied, suggesting that additional loci will be found. 13