An unanticipated copy number variant ofchromosome 15 disrupting SMAD3 reveals a three-generation family at serious risk for aortic dissection

作者：Hilhorst Hofstee Y^*; Scholte A J H A; Rijlaarsdam M E B; van Haeringen A; Kroft L J; Reijnierse M; Ruivenkamp C A L; Versteegh M I M; Pals G; Breuning M H

来源：Clinical Genetics, 2013, 83(4): 337-344.

DOI：10.1111/j.1399-0004.2012.01931.x

• aortic aneurysm
• aortic dissection
• copy number variant
• osteoarthritis
• SMAD3

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.

• 出版日期2013-4