De Novo Damaging Variants, Clinical Phenotypes, and Post-Operative Outcomes in Congenital Heart Disease.

Adolescent Child Child, Preschool Chromosomes, Human, Pair 15 Chromosomes, Human, Pair 3 DNA Copy Number Variations Female Heart Defects, Congenital / genetics Heart Transplantation Humans Infant Kaplan-Meier Estimate Machine Learning Male Odds Ratio Phenotype Proportional Hazards Models Exome Sequencing
congenital heart disease genomics heart transplantation mortality survival

Journal

Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113

Informations de publication

Date de publication:
08 2020
Historique:
entrez: 20 8 2020
pubmed: 20 8 2020
medline: 27 10 2021
Statut: ppublish

Résumé

De novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown. We studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network). Two hundred ninety-four patients (11.7%) had clinically significant de novo variants. Patients with de novo damaging variants were 2.4 times more likely to have extra-cardiac anomalies ( In patients with congenital heart disease undergoing open-heart surgery, de novo variants were associated with worse transplant-free survival and longer times on the ventilator. De novo variants were most strongly associated with adverse outcomes among patients without extra-cardiac anomalies, suggesting a benefit for preoperative genetic testing even when genetic abnormalities are not suspected during routine clinical practice. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01196182.

Sections du résumé

BACKGROUND
De novo genic and copy number variants are enriched in patients with congenital heart disease, particularly those with extra-cardiac anomalies. The impact of de novo damaging variants on outcomes following cardiac repair is unknown.
METHODS
We studied 2517 patients with congenital heart disease who had undergone whole-exome sequencing as part of the CHD GENES study (Congenital Heart Disease Genetic Network).
RESULTS
Two hundred ninety-four patients (11.7%) had clinically significant de novo variants. Patients with de novo damaging variants were 2.4 times more likely to have extra-cardiac anomalies (
CONCLUSIONS
In patients with congenital heart disease undergoing open-heart surgery, de novo variants were associated with worse transplant-free survival and longer times on the ventilator. De novo variants were most strongly associated with adverse outcomes among patients without extra-cardiac anomalies, suggesting a benefit for preoperative genetic testing even when genetic abnormalities are not suspected during routine clinical practice. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01196182.

Identifiants

DOI: 10.1161/CIRCGEN.119.002836 PMID: 32812804 PMC: PMC7439931
pubmed: 32812804
doi: 10.1161/CIRCGEN.119.002836
pmc: PMC7439931
mid: NIHMS1612434
doi:

Banques de données

ClinicalTrials.gov
['NCT01196182']

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e002836

Subventions

Organisme : NHLBI NIH HHS
ID : T32 HL007572
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098162
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098153
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL153009
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006504
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000003
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL128761
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098123
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL128711
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL098147
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098147
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098163
Pays : United States
Organisme : NHLBI NIH HHS
ID : UM1 HL098162
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL098188
Pays : United States

Références

J Thorac Cardiovasc Surg. 2014 Oct;148(4):1597-605
pubmed: 24629220
PLoS Genet. 2012;8(8):e1002843
pubmed: 22912587
J Pediatr. 2008 Dec;153(6):807-13
pubmed: 18657826
J Med Genet. 2008 Nov;45(11):704-9
pubmed: 18713793
Nature. 2013 Jun 13;498(7453):220-3
pubmed: 23665959
Circ Res. 2014 Oct 24;115(10):884-896
pubmed: 25205790
Circulation. 2016 Feb 2;133(5):474-83
pubmed: 26683488
PLoS Genet. 2012 Sep;8(9):e1002903
pubmed: 22969434
Hum Genet. 2014 Jan;133(1):11-27
pubmed: 23979609
Nat Genet. 2009 Aug;41(8):931-5
pubmed: 19597493
J Thorac Cardiovasc Surg. 2016 Apr;151(4):1147-51.e4
pubmed: 26704054
N Engl J Med. 2015 Jul 2;373(1):35-47
pubmed: 26132940
Science. 2015 Dec 4;350(6265):1262-6
pubmed: 26785492
Circ Cardiovasc Genet. 2015 Feb;8(1):74-81
pubmed: 25561045
Congenit Heart Dis. 2011 Nov-Dec;6(6):592-602
pubmed: 22010865
Eur Heart J. 2007 Nov;28(22):2778-84
pubmed: 17384091
Circ Res. 2013 Feb 15;112(4):707-20
pubmed: 23410880
Nat Genet. 2016 Sep;48(9):1060-5
pubmed: 27479907
Nat Genet. 2017 Nov;49(11):1593-1601
pubmed: 28991257
Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2915-20
pubmed: 21282601
Pediatr Res. 2008 Oct;64(4):358-63
pubmed: 18535492
Am J Hum Genet. 2012 Sep 7;91(3):489-501
pubmed: 22939634
Natl Vital Stat Rep. 2013 Dec 18;62(8):1-26
pubmed: 24735562
Circ Cardiovasc Genet. 2013 Oct;6(5):444-51
pubmed: 24021551
J Am Coll Cardiol. 2011 Nov 15;58(21):2241-7
pubmed: 22078432
J Thorac Cardiovasc Surg. 2013 Oct;146(4):868-73
pubmed: 23312975
J Stat Softw. 2011 Mar;39(5):1-13
pubmed: 27065756

Auteurs

Marko T Boskovski (MT)

Department of Cardiac Surgery (M.T.B., M.N., J.E.M.), Harvard Medical School, MA.
Department of Cardiology (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.
Boston Children's Hospital and Department of Surgery (M.T.B., M.N., J.E.M.), Harvard Medical School, MA.
Department of Pediatrics (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.
Division of Cardiac Surgery, Department of Surgery (M.T.B.), Harvard Medical School, MA.
Department of Genetics (M.T.B., J.H., S.M., A.T., J.G., J.G.S., C.E.S.), Harvard Medical School, MA.

Jason Homsy (J)

Department of Genetics (M.T.B., J.H., S.M., A.T., J.G., J.G.S., C.E.S.), Harvard Medical School, MA.

Meena Nathan (M)

Department of Cardiac Surgery (M.T.B., M.N., J.E.M.), Harvard Medical School, MA.
Boston Children's Hospital and Department of Surgery (M.T.B., M.N., J.E.M.), Harvard Medical School, MA.

Lynn A Sleeper (LA)

Department of Cardiology (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.
Department of Pediatrics (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.

Sarah Morton (S)

Department of Newborn Medicine (S.M.), Harvard Medical School, MA.
Department of Genetics (M.T.B., J.H., S.M., A.T., J.G., J.G.S., C.E.S.), Harvard Medical School, MA.

Kathryn B Manheimer (KB)

Mindich Child Health and Development Institute (K.B.M., B.D.G.), Icahn School of Medicine at Mount Sinai, New York, NY.

Angela Tai (A)

Department of Genetics (M.T.B., J.H., S.M., A.T., J.G., J.G.S., C.E.S.), Harvard Medical School, MA.

Joshua Gorham (J)

Department of Genetics (M.T.B., J.H., S.M., A.T., J.G., J.G.S., C.E.S.), Harvard Medical School, MA.

Matthew Lewis (M)

Departments of Pediatrics and Medicine (M.L., W.K.C.), New York-Presbyterian Hospital/Columbia University Medical Center.

Michael Swartz (M)

Department of Cardiac Surgery, University of Rochester, NY (M.S., G.M.A.).

George M Alfieris (GM)

Department of Cardiac Surgery, University of Rochester, NY (M.S., G.M.A.).

Emile A Bacha (EA)

Division of Cardiac, Thoracic, and Vascular Surgery (E.A.B.), New York-Presbyterian Hospital/Columbia University Medical Center.

Mohsen Karimi (M)

Division of Cardiac Surgery (M.K.), Yale University School of Medicine, New Haven, CT.

David Meyer (D)

Department of Pediatric Cardiothoracic Surgery (D.M.), Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park.

Khanh Nguyen (K)

Pediatric Cardiac Surgery, Maria Fareri Children's Hospital, Valhalla, NY (K.N.).

Daniel Bernstein (D)

Department of Pediatrics, Stanford University, CA (D.B.).

Angela Romano-Adesman (A)

Department of Cardiology (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.
Department of Cardiology (A.R.-A.), Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park.

George A Porter (GA)

Department of Pediatrics, University of Rochester Medical Center, NY (G.A.P.).

Elizabeth Goldmuntz (E)

Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia (E.G.).

Wendy K Chung (WK)

Departments of Pediatrics and Medicine (M.L., W.K.C.), New York-Presbyterian Hospital/Columbia University Medical Center.

Deepak Srivastava (D)

Gladstone Institute of Cardiovascular Disease, San Francisco, CA (D.S.).
Roddenberry Stem Cell Center at Gladstone, San Francisco, CA (D.S.).
Departments of Pediatrics and Biochemistry and Biophysics, University of California, San Francisco (D.S.).

Jonathan R Kaltman (JR)

Heart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, NHLBI/NIH, Bethesda, MD (J.R.K.).

Martin Tristani-Firouzi (M)

Department of Pediatrics, University of Utah Medical Center, Salt Lake City (M.T.-F.).

Richard Lifton (R)

Department of Genetics (R.L., M.B.), Yale University School of Medicine, New Haven, CT.

Amy E Roberts (AE)

Department of Pediatrics (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.

J William Gaynor (JW)

Department of Pediatrics (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.
Department of Pediatric Cardiac Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.).

Bruce D Gelb (BD)

Mindich Child Health and Development Institute (K.B.M., B.D.G.), Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Genetics and Genomic Sciences (B.D.G.), Icahn School of Medicine at Mount Sinai, New York, NY.
Department of Pediatrics (B.D.G.), Icahn School of Medicine at Mount Sinai, New York, NY.

Richard Kim (R)

Pediatric Cardiac Surgery, Children's Hospital of Los Angeles, CA (R.K.).

Jonathan G Seidman (JG)

Department of Genetics (M.T.B., J.H., S.M., A.T., J.G., J.G.S., C.E.S.), Harvard Medical School, MA.

Martina Brueckner (M)

Department of Genetics (R.L., M.B.), Yale University School of Medicine, New Haven, CT.
Department of Pediatrics (M.B.), Yale University School of Medicine, New Haven, CT.

John E Mayer (JE)

Department of Cardiac Surgery (M.T.B., M.N., J.E.M.), Harvard Medical School, MA.
Boston Children's Hospital and Department of Surgery (M.T.B., M.N., J.E.M.), Harvard Medical School, MA.

Jane W Newburger (JW)

Department of Cardiology (M.T.B., L.A.S., A.E.R., J.W.N.), Harvard Medical School, MA.

Christine E Seidman (CE)

Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital (C.E.S.), Harvard Medical School, MA.
Department of Genetics (M.T.B., J.H., S.M., A.T., J.G., J.G.S., C.E.S.), Harvard Medical School, MA.
Howard Hughes Medical Institute, Chevy Chase, MD (C.E.S.).

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Enfant d'âge préscolaire › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 13-15 › Chromosomes humains de la paire 15 › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 1-3 › Chromosomes humains de la paire 3 › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Variation structurale du génome › Variations de nombre de copies de segment d'ADN › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › Malformations cardiovasculaires › Cardiopathies congénitales › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation d'organe › Transplantation cardiaque › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Personnes › Tranches d'âge › Nourrisson › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Estimation de Kaplan-Meier › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Sciences de l'information › Méthodologies informatiques › Algorithmes › Intelligence artificielle › Apprentissage machine › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Odds ratio › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Modèles des risques proportionnels › De Novo Damaging Variants, Clinical...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › De Novo Damaging Variants, Clinical...