Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome

被引：0
作者：
Elisabeth E. Mlynarski
Michael Xie
Deanne Taylor
Molly B. Sheridan
Tingwei Guo
Silvia E. Racedo
Donna M. McDonald-McGinn
Eva W. C. Chow
Jacob Vorstman
Ann Swillen
Koen Devriendt
Jeroen Breckpot
Maria Cristina Digilio
Bruno Marino
Bruno Dallapiccola
Nicole Philip
Tony J. Simon
Amy E. Roberts
Małgorzata Piotrowicz
Carrie E. Bearden
Stephan Eliez
Doron Gothelf
Karlene Coleman
Wendy R. Kates
Marcella Devoto
Elaine Zackai
Damian Heine- Suñer
Elizabeth Goldmuntz
Anne S. Bassett
Bernice E. Morrow
Beverly S. Emanuel
机构：
[1] The Children’s Hospital of Philadelphia,Division of Human Genetics
[2] Children’s Hospital of Philadelphia,Department of Biomedical and Health Informatics
[3] Albert Einstein College of Medicine,Department of Genetics
[4] University of Pennsylvania,Department of Pediatrics, Perelman School of Medicine
[5] University of Toronto,Clinical Genetics Research Program, Centre for Addiction and Mental Health and Department of Psychiatry
[6] University Medical Center Utrecht,Department of Psychiatry, Brain Center Rudolf Magnus
[7] University of Leuven,Center for Human Genetics
[8] Bambino Gesù Hospital,Medical Genetics
[9] La Sapienza University of Rome,Lorillard Spencer Cenci Foundation and Department of Pediatrics
[10] AP-HM and University of Mediterranee,Department of Medical Genetics, Timone Children’s Hospital
[11] University of California,Department of Psychiatry and Behavioral Sciences, M.I.N.D. Institute
[12] Boston Children’s Hospital,Department of Cardiology and Division of Genetics
[13] Polish Mother’s Memorial Hospital,Department of Genetics, Research Institute
[14] University of California,Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior
[15] University of Geneva School of Medicine,Office Médico
[16] Sheba Medical Center, Pédagogique Research Unit, Department of Psychiatry
[17] Tel Aviv University,Edmond and Lily Safra Children’s Hospital
[18] Children’s Healthcare of Atlanta,Sackler Faculty of Medicine
[19] SUNY Upstate Medical University,Marcus Autism Center
[20] University of Pennsylvania,Department of Psychiatry and Behavioral Sciences, and Program in Neuroscience
[21] University of Rome La Sapienza,Department of Biostatistics and Epidemiology, Perelman School of Medicine
[22] Hospital Universitari Son Espases,Department of Molecular Medicine
[23] Children’s Hospital of Philadelphia,Genetics Department
来源：
Human Genetics | 2016年 / 135卷
关键词：
Congenital Heart Defect; Mammalian Phenotype; Rare CNVs; Normal Cardiac Anatomy; Rare Deletion;
D O I：
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中图分类号：
学科分类号：
摘要：
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.
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页码：273 / 285
页数：12
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