Rationale for the Cytogenomics of Cardiovascular Malformations Consortium: A Phenotype Intensive Registry Based Approach

Journal of Cardiovascular Development and Disease

Robert B. Hinton³  Kim L. McBride⁴  Steven B. Bleyl⁷  Neil E. Bowles⁷  William L. Border⁵  Vidu Garg⁴  Teresa A. Smolarek³  Seema R. Lalani¹  Stephanie M. Ware²  Cheryl L. Maslen⁶ 

[1] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; E-Mail:;Departments of Pediatrics and Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA;Divisions of Cardiology and Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA; E-Mails:;Center for Cardiovascular and Pulmonary Research and Heart Center, Nationwide Children’s Hospital and Department of Pediatrics, Ohio State University, Columbus, OH 43205, USA; E-Mails:;Division of Cardiology, Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA; E-Mail:Divisions of Cardiology and Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA;;Division of Pediatric Cardiology, University of Utah School of Medicine, Salt Lake City, UT 84132, USA; E-Mails:

关键词: genetics;    genomics;    pediatrics;    cardiovascular malformation;    registry;    chromosome microarray;    copy number variation;   

DOI  :  10.3390/jcdd2020076

来源: mdpi

【 摘 要 】

Cardiovascular malformations (CVMs) are the most common birth defect, occurring in 1%–5% of all live births. Although the genetic contribution to CVMs is well recognized, the genetic causes of human CVMs are identified infrequently. In addition, a failure of systematic deep phenotyping of CVMs, resulting from the complexity and heterogeneity of malformations, has obscured genotype-phenotype correlations and contributed to a lack of understanding of disease mechanisms. To address these knowledge gaps, we have developed the Cytogenomics of Cardiovascular Malformations (CCVM) Consortium, a multi-site alliance of geneticists and cardiologists, contributing to a database registry of submicroscopic genetic copy number variants (CNVs) based on clinical chromosome microarray testing in individuals with CVMs using detailed classification schemes. Cardiac classification is performed using a modification to the National Birth Defects Prevention Study approach, and non-cardiac diagnoses are captured through ICD-9 and ICD-10 codes. By combining a comprehensive approach to clinically relevant genetic analyses with precise phenotyping, the Consortium goal is to identify novel genomic regions that cause or increase susceptibility to CVMs and to correlate the findings with clinical phenotype. This registry will provide critical insights into genetic architecture, facilitate genotype-phenotype correlations, and provide a valuable resource for the medical community.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.