Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting.

作者: Bulat A. Ziganshin , Allison E. Bailey , Celinez Coons , Daniel Dykas , Paris Charilaou

DOI: 10.1016/J.ATHORACSUR.2015.04.106

关键词:

摘要: Background Hereditary factors play an important etiologic role in thoracic aortic aneurysm and dissection (TAAD), with a number of genes proven to predispose this condition. We initiated clinical program for routine genetic testing individuals TAAD by whole exome sequencing (WES). Here we present our initial results. Methods The WES was performed 102 patients (mean age 56.8 years; range 13 83; 70 males [68.6%]) TAAD. following 21-gene panel tested WES: ACTA2, ADAMTS10, COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ELN, FBLN4, FLNA, FBN1, FBN2, MYH11, MYLK, NOTCH1, PRKG1, SLC2A10, SMAD3, TGFB2, TGFBR1, TGFBR2. Results Seventy-four (72.5%) had no medically alterations. Four (3.9%) deleterious mutation identified the FLNA genes. Twenty-two (21.6%) previously unreported suspicious variants unknown significance were 1 or more genes: FBN1 (n = 5); MYH11 4); ACTA2 2); COL1A1 TGFBR1 COL3A1 1); COL5A1 COL5A2 NOTCH1 PRKG1 TGFBR3 1). Identified mutations implications management. Conclusions Routine screening provides information that enables genetically personalized care permits identification novel responsible pathology. Analysis large data sets include associated features will help define mutational spectrum known underlying phenotype potential identify new candidate loci.

参考文章(23)
Lut Van Laer, Harry Dietz, Bart Loeys, Loeys-Dietz Syndrome Advances in Experimental Medicine and Biology. ,vol. 802, pp. 95- 105 ,(2014) , 10.1007/978-94-007-7893-1_7
Laurence Campens, Julie De Backer, Anne De Paepe, Genes in thoracic aortic aneurysms/dissections - do they matter? Annals of cardiothoracic surgery. ,vol. 2, pp. 73- 82 ,(2013) , 10.3978/J.ISSN.2225-319X.2012.12.01
John A. Elefteriades, Pawel Pomianowski, The genetics and genomics of thoracic aortic disease Annals of cardiothoracic surgery. ,vol. 2, pp. 271- 279 ,(2013) , 10.3978/J.ISSN.2225-319X.2013.05.12
John A. Elefteriades, Pawel Pomianowski, Practical Genetics of Thoracic Aortic Aneurysm Progress in Cardiovascular Diseases. ,vol. 56, pp. 57- 67 ,(2013) , 10.1016/J.PCAD.2013.06.002
Wei-Qi He, Min-Sheng Zhu, Stephan Offermanns, Dawna Gilchrist, John Elefteriades, James T. Stull, Dianna M. Milewicz, Li Wang, Dong-chuan Guo, Jiumei Cao, Limin Gong, Kristine E. Kamm, Ellen Regalado, Li Li, Sanjay Shete, Mutations in Myosin Light Chain Kinase Cause Familial Aortic Dissections American Journal of Human Genetics. ,vol. 87, pp. 701- 707 ,(2010) , 10.1016/J.AJHG.2010.10.006
Reed Pyeritz, , Guillaume Jondeau, Rocio Moran, Julie De Backer, Eloisa Arbustini, Anne De Paepe, Dianna Milewicz, Loeys-Dietz syndrome is a specific phenotype and not a concomitant of any mutation in a gene involved in TGF-β signaling Genetics in Medicine. ,vol. 16, pp. 641- 642 ,(2014) , 10.1038/GIM.2014.63
Leslie G. Biesecker, Robert C. Green, Diagnostic Clinical Genome and Exome Sequencing The New England Journal of Medicine. ,vol. 370, pp. 2418- 2425 ,(2014) , 10.1056/NEJMRA1312543
Michael A Coady, Ryan R Davies, Michele Roberts, Lee J Goldstein, Matthew J Rogalski, John A Rizzo, Graeme L Hammond, Gary S Kopf, John A Elefteriades, Familial Patterns of Thoracic Aortic Aneurysms Archives of Surgery. ,vol. 134, pp. 361- 367 ,(1999) , 10.1001/ARCHSURG.134.4.361
Alan Biddinger, Marnie Rocklin, Joseph Coselli, Dianna M. Milewicz, Familial thoracic aortic dilatations and dissections: A case control study Journal of Vascular Surgery. ,vol. 25, pp. 506- 511 ,(1997) , 10.1016/S0741-5214(97)70261-1