OBJECTIVES: Genetic defects associated with bicuspid aortopathy have been infrequently analysed. Our goal was to examine the prevalence of rare genetic variants in patients with a bicuspid aortic valve (BAV) with a root phenotype using next-generation sequencing technology. METHODS: We investigated a total of 124 patients with BAV with a root dilatation phenotype who underwent aortic valve ± proximal aortic surgery at a single institution (BAV database, n = 812) during a 20-year period (1995-2015). Cross-sectional follow-up revealed 63 (51%) patients who were still alive and willing to participate. Systematic follow-up visits were scheduled from March to December 2015 and included aortic imaging as well as peripheral blood sampling for genetic testing. Next-generation sequencing libraries were prepared using a custom-made HaloPlex HS gene panel and included 20 candidate genes known to be associated with aortopathy and BAV. The primary end-point was the prevalence of genetic defects in our study cohort. RESULTS: A total of 63 patients (mean age 46 ± 10 years, 92% men) with BAV root phenotype and mean post-aortic valve replacement follow-up of 10.3 ± 4.9 years were included. Our genetic analysis yielded a wide spectrum of rare, potentially or likely pathogenic variants in 19 (30%) patients, with NOTCH1 variants being the most common ( n = 6). Moreover, deleterious variants were revealed in AXIN1 ( n = 3), NOS3 ( n = 3), ELN ( n = 2), FBN1 ( n = 2) , FN1 ( n = 2) and rarely in other candidate genes. CONCLUSIONS: Our preliminary study demonstrates a high prevalence and a wide spectrum of rare genetic variants in patients with the BAV root phenotype, indicative of the potentially congenital origin of associated aortopathy in this specific BAV cohort.
OBJECTIVES:Genetic defects associated with bicuspid aortopathy have been infrequently analysed. Our goal was to examine the prevalence of rare genetic variants in patients with a bicuspid aortic valve (BAV) with a root phenotype using next-generation sequencing technology. METHODS: We investigated a total of 124 patients with BAV with a root dilatation phenotype who underwent aortic valve ± proximal aortic surgery at a single institution (BAV database, n = 812) during a 20-year period (1995-2015). Cross-sectional follow-up revealed 63 (51%) patients who were still alive and willing to participate. Systematic follow-up visits were scheduled from March to December 2015 and included aortic imaging as well as peripheral blood sampling for genetic testing. Next-generation sequencing libraries were prepared using a custom-made HaloPlex HS gene panel and included 20 candidate genes known to be associated with aortopathy and BAV. The primary end-point was the prevalence of genetic defects in our study cohort. RESULTS: A total of 63 patients (mean age 46 ± 10 years, 92% men) with BAV root phenotype and mean post-aortic valve replacement follow-up of 10.3 ± 4.9 years were included. Our genetic analysis yielded a wide spectrum of rare, potentially or likely pathogenic variants in 19 (30%) patients, with NOTCH1 variants being the most common ( n = 6). Moreover, deleterious variants were revealed in AXIN1 ( n = 3), NOS3 ( n = 3), ELN ( n = 2), FBN1 ( n = 2) , FN1 ( n = 2) and rarely in other candidate genes. CONCLUSIONS: Our preliminary study demonstrates a high prevalence and a wide spectrum of rare genetic variants in patients with the BAV root phenotype, indicative of the potentially congenital origin of associated aortopathy in this specific BAV cohort.
Authors: Hector I Michelena; Alessandro Della Corte; Arturo Evangelista; Joseph J Maleszewski; William D Edwards; Mary J Roman; Richard B Devereux; Borja Fernández; Federico M Asch; Alex J Barker; Lilia M Sierra-Galan; Laurent De Kerchove; Susan M Fernandes; Paul W M Fedak; Evaldas Girdauskas; Victoria Delgado; Suhny Abbara; Emmanuel Lansac; Siddharth K Prakash; Malenka M Bissell; Bogdan A Popescu; Michael D Hope; Marta Sitges; Vinod H Thourani; Phillippe Pibarot; Krishnaswamy Chandrasekaran; Patrizio Lancellotti; Michael A Borger; John K Forrest; John Webb; Dianna M Milewicz; Raj Makkaar; Martin B Leon; Stephen P Sanders; Michael Markl; Victor A Ferrari; William C Roberts; Jae-Kwan Song; Philipp Blanke; Charles S White; Samuel Siu; Lars G Svensson; Alan C Braverman; Joseph Bavaria; Thoralf M Sundt; Gebrine El Khoury; Ruggero De Paulis; Maurice Enriquez-Sarano; Jeroen J Bax; Catherine M Otto; Hans-Joachim Schäfers Journal: Radiol Cardiothorac Imaging Date: 2021-07-22
Authors: Radoslaw Marek Debiec; Stephen E Hamby; Peter D Jones; Kassem Safwan; Michael Sosin; Simon Lee Hetherington; David Sprigings; David Sharman; Kelvin Lee; Pegah Salahshouri; Nigel Wheeldon; Andrew Chukwuemeka; Vasiliki Boutziouka; Mohamed Elamin; Sue Coolman; Manish Asiani; Shireen Kharodia; Gregory J Skinner; Nilesh J Samani; Tom R Webb; Aidan P Bolger Journal: Heart Date: 2022-06-24 Impact factor: 7.365
Authors: Carmela R Balistreri; Silvio Buffa; Alberto Allegra; Calogera Pisano; Giovanni Ruvolo; Giuseppina Colonna-Romano; Domenico Lio; Giuseppe Mazzesi; Sonia Schiavon; Ernesto Greco; Silvia Palmerio; Sebastiano Sciarretta; Elena Cavarretta; Antonino G M Marullo; Giacomo Frati Journal: Oxid Med Cell Longev Date: 2018-04-05 Impact factor: 6.543
Authors: Alexander J Fletcher; Maaz B J Syed; Timothy J Aitman; David E Newby; Niki L Walker Journal: Circulation Date: 2020-05-11 Impact factor: 29.690