Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome
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- 作者：Elisabeth E. Mlynarski ; Michael Xie ; Deanne Taylor ; Molly B. Sheridan…
- 刊名：Human Genetics
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：135
- 期：3
- 页码：273-285
- 全文大小：907 KB
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Michael Xie (2)
Deanne Taylor (2)
Molly B. Sheridan (1)
Tingwei Guo (3)
Silvia E. Racedo (3)
Donna M. McDonald-McGinn (1) (4)
Eva W. C. Chow (5)
Jacob Vorstman (6)
Ann Swillen (7)
Koen Devriendt (7)
Jeroen Breckpot (7)
Maria Cristina Digilio (8)
Bruno Marino (9)
Bruno Dallapiccola (8)
Nicole Philip (10)
Tony J. Simon (11)
Amy E. Roberts (12)
Małgorzata Piotrowicz (13)
Carrie E. Bearden (14)
Stephan Eliez (15)
Doron Gothelf (16) (17)
Karlene Coleman (18)
Wendy R. Kates (19)
Marcella Devoto (1) (20) (21) (4)
Elaine Zackai (1) (4)
Damian Heine- Suñer (22)
Elizabeth Goldmuntz (23) (4)
Anne S. Bassett (5)
Bernice E. Morrow (3)
Beverly S. Emanuel (1) (4)
The International Chromosome 22q11.2 Consortium
1. Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA
2. Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA
3. Department of Genetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA
4. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
5. Clinical Genetics Research Program, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada
6. Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, 3584, Utrecht, The Netherlands
7. Center for Human Genetics, University of Leuven, 3000, Leuven, Belgium
8. Medical Genetics, Bambino Gesù Hospital, 00165, Rome, Italy
9. Lorillard Spencer Cenci Foundation and Department of Pediatrics, La Sapienza University of Rome, 00165, Rome, Italy
10. Department of Medical Genetics, Timone Children’s Hospital, AP-HM and University of Mediterranee, 13005, Marseille, France
11. Department of Psychiatry and Behavioral Sciences, M.I.N.D. Institute, University of California, Sacramento, CA, 95817, USA
12. Department of Cardiology and Division of Genetics, Boston Children’s Hospital, Boston, MA, 02115, USA
13. Department of Genetics, Research Institute, Polish Mother’s Memorial Hospital, 93-338, Lodz, Poland
14. Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, 90095, USA
15. Office Médico- Pédagogique Research Unit, Department of Psychiatry, University of Geneva School of Medicine, 1211, Geneva 8, Switzerland
16. Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, Israel
17. Sackler Faculty of Medicine, Tel Aviv University, 52621, Tel Aviv, Israel
18. Marcus Autism Center, Children’s Healthcare of Atlanta, Atlanta, GA, 30322, USA
19. Department of Psychiatry and Behavioral Sciences, and Program in Neuroscience, SUNY Upstate Medical University, Syracuse, NY, 13210, USA
20. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA
21. Department of Molecular Medicine, University of Rome La Sapienza, 00185, Rome, Italy
22. Genetics Department, Hospital Universitari Son Espases, 07020, Palma de Mallorca, Spain
23. Division of Cardiology, Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA - 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Human Genetics
Molecular Medicine
Internal Medicine
Metabolic Diseases - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-1203
文摘
The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60–75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect. The etiology of the cardiac phenotypic variability is not currently known for the majority of patients. We hypothesized that rare copy number variants (CNVs) outside the 22q11.2 deleted region may modify the risk of being born with a CHD in this sensitized population. Rare CNV analysis was performed using Affymetrix SNP Array 6.0 data from 946 22q11DS subjects with CHDs (n = 607) or with normal cardiac anatomy (n = 339). Although there was no significant difference in the overall burden of rare CNVs, an overabundance of CNVs affecting cardiac-related genes was detected in 22q11DS individuals with CHDs. When the rare CNVs were examined with regard to gene interactions, specific cardiac networks, such as Wnt signaling, appear to be overrepresented in 22q11DS CHD cases but not 22q11DS controls with a normal heart. Collectively, these data suggest that CNVs outside the 22q11.2 region may contain genes that modify risk for CHDs in some 22q11DS patients.