Genetic abnormalities in bicuspid aortic valve root phenotype: preliminary results

TY - JOUR

T1 - Genetic abnormalities in bicuspid aortic valve root phenotype: preliminary results

AU - Girdauskas, Evaldas

AU - Geist, Lisa

AU - Disha, Kushtrim

AU - Kazakbaev, Iliaz

AU - Groß, Tatiana

AU - Schulz, Solveig

AU - Ungelenk, Martin

AU - Kuntze, Thomas

AU - Reichenspurner, Hermann

AU - Kurth, Ingo

N1 - © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aortic Valve/abnormalities

KW - Bicuspid Aortic Valve Disease

KW - Cross-Sectional Studies

KW - DNA/genetics

KW - Echocardiography

KW - Female

KW - Follow-Up Studies

KW - Forecasting

KW - Gene Library

KW - Genetic Testing

KW - Heart Valve Diseases/diagnosis

KW - Heart Valve Prosthesis Implantation

KW - Humans

KW - Magnetic Resonance Imaging, Cine

KW - Male

KW - Middle Aged

KW - Phenotype

KW - Polymorphism, Genetic

KW - Retrospective Studies

KW - Young Adult

U2 - 10.1093/ejcts/ezx065

DO - 10.1093/ejcts/ezx065

M3 - SCORING: Journal article

C2 - 28387797

VL - 52

SP - 156

EP - 162

JO - EUR J CARDIO-THORAC

JF - EUR J CARDIO-THORAC

SN - 1010-7940

IS - 1

ER -