De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies

Author:

Homsy Jason12,Zaidi Samir3,Shen Yufeng4,Ware James S.156,Samocha Kaitlin E.17,Karczewski Konrad J.17,DePalma Steven R.18,McKean David1,Wakimoto Hiroko1,Gorham Josh1,Jin Sheng Chih3,Deanfield John9,Giardini Alessandro9,Porter George A.10,Kim Richard11,Bilguvar Kaya312,López-Giráldez Francesc12,Tikhonova Irina12,Mane Shrikant12,Romano-Adesman Angela13,Qi Hongjian414,Vardarajan Badri15,Ma Lijiang16,Daly Mark17,Roberts Amy E.17,Russell Mark W.18,Mital Seema19,Newburger Jane W.20,Gaynor J. William21,Breitbart Roger E.20,Iossifov Ivan22,Ronemus Michael22,Sanders Stephan J.23,Kaltman Jonathan R.24,Seidman Jonathan G.1,Brueckner Martina3,Gelb Bruce D.25,Goldmuntz Elizabeth2627,Lifton Richard P.328,Seidman Christine E.1829,Chung Wendy K.30

Affiliation:

1. Department of Genetics, Harvard Medical School, Boston, MA, USA.

2. Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.

3. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.

4. Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, USA.

5. NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation and Trust and Imperial College London, London, UK.

6. National Heart & Lung Institute, Imperial College London, London, UK.

7. Analytical and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.

8. Howard Hughes Medical Institute, Harvard University, Boston, MA, USA.

9. Department of Cardiology, University College London and Great Ormond Street Hospital, London, UK.

10. Department of Pediatrics, University of Rochester Medical Center, The School of Medicine and Dentistry, Rochester, NY, USA.

11. Section of Cardiothoracic Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.

12. Yale Center for Genome Analysis, Yale University, New Haven, CT, USA.

13. Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, NY, USA.

14. Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY, USA.

15. Department of Neurology, Columbia University Medical Center, New York, NY, USA.

16. Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.

17. Department of Cardiology, Children's Hospital Boston, Boston, MA, USA.

18. Division of Pediatric Cardiology, University of Michigan, Ann Arbor, MI, USA.

19. Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

20. Department of Cardiology, Boston Children's Hospital, Boston, MA, USA.

21. Department of Pediatric Cardiac Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

22. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.

23. Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA.

24. Heart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, NHLBI/NIH, Bethesda, MD, USA.

25. Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

26. Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

27. Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

28. Howard Hughes Medical Institute, Yale University, New Haven, CT, USA.

29. Cardiovascular Division, Brigham & Women’s Hospital, Harvard University, Boston, MA, USA.

30. Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA.

Abstract

Putting both heart and brain at risk For reasons that are unclear, newborns with congenital heart disease (CHD) have a high risk of neurodevelopmental disabilities. Homsy et al. performed exome sequence analysis of 1200 CHD patients and their parents to identify spontaneously arising (de novo) mutations. Patients with both CHD and neurodevelopmental disorders had a much higher burden of damaging de novo mutations, particularly in genes with likely roles in both heart and brain development. Thus, clinical genotyping of patients with CHD may help to identify those at greatest risk of neurodevelopmental disabilities, allowing surveillance and early intervention. Science , this issue p. 1262

Funder

Howard Hughes Medical Institute

National Heart, Lung, and Blood Institute

Simons Foundation for Autism Research

Wellcome Trust

Harvard Medical School

Heart and Stroke Foundation of Ontario

British Heart Foundation

Arthritis Research UK

Academy of Medical Sciences

Imperial College London

Leducq Foundation

National Human Genome Research Institute of the National Institutes of Health (NIH)

National Research Science Award

NIHR Cardiovascular Biomedical Research Unit at Royal Brompton

Harefield NHS Foundation Trust

Ted Roger Centre for Heart Research

Kostin Family Innovation Fund

Aaron Stern Professorship at the University of Michigan

Braylon’s Gift of Hope Fund

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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