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

American Association for the Advancement of Science (AAAS) - Tập 350 Số 6265 - Trang 1262-1266 - 2015
Jason Homsy1,2, Samir Zaidi3, Yufeng Shen4, James S. Ware2,5,6, Kaitlin E. Samocha7,2, Jakub Karczewski7,2, Steven R. DePalma2,8, David McKean2, Hiroko Wakimoto2, Josh Gorham2, Sheng Chih Jin3, John Deanfield9, Anna Giardini9, George A. Porter10, Richard Kim11, Kaya Bilgüvar3,12, Francesc López‐Giráldez12, Irina Tikhonova12, Shrikant Mane12, Angela Romano-Adesman13, Hongjian Qi14,4, Badri N. Vardarajan15, Lijiang Ma16, Mark J. Daly7,2, Amy E. Roberts17, Mark W. Russell18, Seema Mital19, Jane W. Newburger20, J. William Gaynor21, Roger E. Breitbart20, Ivan Iossifov22, Michael Ronemus22, Stephan Sanders23, Jonathan R. Kaltman24, Jonathan G. Seidman2, Martina Brueckner3, Bruce D. Gelb25, Elizabeth Goldmuntz26,27, Richard P. Lifton3,28, Christine E. Seidman29,2,8, Wendy K. Chung30
1Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
2Department of Genetics, Harvard Medical School, Boston, MA, USA.
3Department of Genetics, Yale University School of Medicine, New Haven, CT, USA
4Departments of Systems Biology and Biomedical Informatics, Columbia University Medical Center, New York, NY, USA.
5NIHR Cardiovascular Biomedical Research Unit at Royal Brompton & Harefield NHS Foundation and Trust and Imperial College London, London, UK.
6National Heart & Lung Institute, Imperial College London, London, UK.
7Analytical and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston MA, USA.
8Howard Hughes Medical Institute, Harvard University, Boston, MA, USA
9Department of Cardiology, University College London and Great Ormond Street Hospital, London, UK.
10Department of Pediatrics, University of Rochester Medical Center, The School of Medicine and Dentistry, Rochester, NY, USA.
11Section of Cardiothoracic Surgery, University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
12Yale Center for Genome Analysis, Yale University, New Haven, CT, USA
13Steven and Alexandra Cohen Children's Medical Center of New York, New Hyde Park, NY, USA.
14Department of Applied Physics and Applied Mathematics, Columbia University, New York, NY, USA
15Department of Neurology, Columbia University Medical Center, New York, NY, USA
16Department of Pediatrics, Columbia University Medical Center, New York, NY, USA
17Department of Cardiology, Children's Hospital Boston, Boston, MA, USA
18Division of Pediatric Cardiology, University of Michigan, Ann Arbor, MI, USA
19Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
20Department of Cardiology, Boston Children's Hospital, Boston, MA USA
21Department of Pediatric Cardiac Surgery, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
22Cold Spring Harbor Laboratory, Cold Spring Harbor, NY USA
23Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA
24Heart Development and Structural Diseases Branch, Division of Cardiovascular Sciences, NHLBI/NIH, Bethesda, MD, USA.
25Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
26Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
27Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, Pa, USA
28Howard Hughes Medical Institute, Yale University, New Haven, CT, USA
29Cardiovascular Division, Brigham & Women’s Hospital, Harvard University, Boston, MA, USA.
30Departments of Pediatrics and Medicine, Columbia University Medical Center, New York, NY, USA

Tóm tắt

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

Từ khóa


Tài liệu tham khảo

10.4103/0974-2069.132474

10.1161/CIR.0b013e318265ee8a

10.1542/peds.2014-3825

10.1161/CIRCRESAHA.111.300297

10.1056/NEJMoa0912461

10.1038/nature12141

10.1038/nature13908

10.1038/nature10945

10.1038/ng.835

10.1038/ng.3050

10.1093/hmg/ddu733

10.1161/CIRCRESAHA.115.304458

10.1016/j.ydbio.2011.08.025

10.1038/onc.2013.50

10.1016/j.jacc.2011.04.046

10.1038/nsmb.1545

10.1016/j.ajhg.2014.08.013

10.1056/NEJMoa1206524

10.1016/S0140-6736(12)61480-9

10.1038/nature13772

10.1038/ng.902

10.1038/nature14135

10.1016/j.jpeds.2014.05.019

10.1038/ng.806

10.1002/humu.22376

10.1093/bioinformatics/btp324

Ware J. S., Samocha K. E., Homsy J., Daly M. J., Interpreting de novo variation in human disease using denovolyzeR. Curr. Protoc. Hum. Genet. 87, 1–15, 15 (2015).26439716

10.1093/nar/gkr378