Genetic testing for bicuspid aortic valve

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Bicuspid aortic valve (BAV) is a congenital defect in which the aortic valve has two rather than three leaflets. In many patients valve function may be normal but valve decompensation may occur due to other associated congenital abnormalities and secondary valve and aortic complications. Decompensation manifests as stenosis or regurgitation and thoracic aortic aneurysm and dissection. Cystic medial necrosis plays an important role in the pathogenesis of BAV. Prevalence of BAV is estimated at 0.5-2.0%. In children, 70-85% of stenotic aortic valves are bicuspid, compared to at least 50% in adults. BAV has autosomal dominant inheritance. This Utility Gene Test was developed on the basis of an analysis of the literature and existing diagnostic protocols. It is useful for confirming diagnosis, as well as for differential diagnosis, couple risk assessment and access to clinical trials.

1. Cripe L, Andelfinger G, Martin LJ, Shooner K, Benson DW. Bicuspid aortic valve is heritable. J Am Coll Cardiol 2004; 7;44(1): 138-43.

2. Atkins SK, Sucosky P. Etiology of bicuspid aortic valve disease: Focus on hemodynamics. World Journal of Cardiology 2014; 6(12): 1227-33.

3. Freeze SL, Landis BJ, Ware SM, Helm BM. Bicuspid Aortic Valve: a Review with Recommendations for Genetic Counseling. Journal of genetic counseling 2016; 25(6): 1171-78.

4. Braverman AC, Güven H, Beardslee MA, Makan M, Kates AM, Moon MR. The bicuspid aortic valve. Curr Probl Cardiol 2005; 30(9): 470-22.

5. Roberts WC. The congenitally bicuspid aortic valve. A study of 85 autopsy cases. Am J Cardiol 1970; 26(1): 72-83.

6. Steinberger J, Moller JH, Berry JM, Sinaiko AR. Echocardiographic diagnosis of heart disease in apparently healthy adolescents. Pediatrics 2000; 105(4 Pt 1): 815-18.

7. Mack G, Silberbach M. Aortic and pulmonary stenosis. Pediatr Rev 2000; 21: 79–85.

8. Ward C. Clinical significance of the bicuspid aortic valve. Heart 2000; 83(1): 81-85.

9. Michelena HI, Desjardins VA, Avierinos JF, Russo A, Nkomo VT, Sundt TM, Pellikka PA, Tajik AJ, Enriquez-Sarano M. Natural history of asymptomatic patients with normally functioning or minimally dysfunctional bicuspid aortic valve in the community. Circulation 2008; 117(21): 2776-84.

10. Zuberbuhler JR. Aortic stenosis. Clinical Diagnosis in Pediatric Cardiology. London, England: Churchill Livingstone 1981; 75-82.

11. Qu XK, Qiu XB, Yuan F, Wang J, Zhao CM, Liu XY, Zhang XL, Li RG, Xu YJ, Hou XM, Fang WY, Liu X, Yang YQ. A novel NKX2.5 loss-of-function mutation associated with congenital bicuspid aortic valve. Am J Cardiol 2014; 15;114(12): 1891-95.

12. Bonachea EM, Zender G, White P, Corsmeier D, Newsom D, Fitzgerald-Butt S, Garg V, McBride KL. Use of a targeted, combinatorial next-generation sequencing approach for the study of bicuspid aortic valve. BMC Med Genomics 2014; 26; 7:56.

13. Abdulkareem N, Smelt J, Jahangiri M. Bicuspid aortic valve aortopathy: genetics, pathophysiology and medical therapy. Interact Cardiovasc Thorac Surg 2013; 17(3): 554-59.

14. Giusti B, Sticchi E, De Cario R, Magi A, Nistri S, Pepe G. Genetic Bases of Bicuspid Aortic Valve: The Contribution of Traditional and High-Throughput Sequencing Approaches on Research and Diagnosis. Front Physiol 2017; 8: 612.

15. Prakash SK, Bossé Y, Muehlschlegel JD, Michelena HI, Limongelli G, Della Corte A, Pluchinotta FR, Russo MG, Evangelista A, Benson DW, Body SC, Milewicz DM; BAVCon Investigators. A roadmap to investigate the genetic basis of bicuspid aortic valve and its complications: insights from the International BAVCon (Bicuspid Aortic Valve Consortium). J Am Coll Cardiol 2014; 64(8): 832-39.

16. Girdauskas E, Geist L, Disha K, Kazakbaev I, Groß T, Schulz S, Ungelenk M, Kuntze T, Reichenspurner H, Kurth I. Genetic abnormalities in bicuspid aortic valve root phenotype: preliminary results. Eur J Cardiothorac Surg 2017; 52(1): 156-62.

17. Lin X, Huo Z, Liu X, Zhang Y, Li L, Zhao H, Yan B, Liu Y, Yang Y, Chen YH. A novel GATA6 mutation in patients with tetralogy of Fallot or atrial septal defect. J Hum Genet 2010; 55(10): 662-67.

18. Bowling KM, Thompson ML, Amaral MD, Finnila CR, Hiatt SM, Engel KL, Cochran JN, Brothers KB, East KM, Gray DE, Kelley WV, Lamb NE, Lose EJ, Rich CA, Simmons S, Whittle JS, Weaver BT, Nesmith AS, Myers RM, Barsh GS, Bebin EM, Cooper GM. Genomic diagnosis for children with intellectual disability and/or developmental delay. Genome Med 2017; 9(1): 43.

19. Quintero-Rivera F, Xi QJ, Keppler-Noreuil KM, Lee JH, Higgins AW, Anchan RM, Roberts AE, Seong IS, Fan X, Lage K, Lu LY, Tao J, Hu X, Berezney R, Gelb BD, Kamp A, Moskowitz IP, Lacro RV, Lu W, Morton CC, Gusella JF, Maas RL. MATR3 disruption in human and mouse associated with bicuspid aortic valve, aortic coarctation and patent ductus arteriosus. Hum Mol Genet 2015; 24(8): 2375-89.

20. Chen B, Gagnon M, Shahangian S, Anderson NL, Howerton DA, Boone JD; Centers for Disease Control and Prevention (CDC). Good Laboratory Practices for Molecular Genetic Testing for Heritable Diseases and Conditions. MMWR Recomm Rep 2009; 58 (RR-6): 1-29.

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