Assessment of large copy number variants in patients with apparently isolated congenital left-sided cardiac lesions reveals clinically relevant genomic events.

Autor: Hanchard NA; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas., Umana LA; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas., D'Alessandro L; Division of Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Azamian M; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas., Poopola M; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas., Morris SA; Division of Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas., Fernbach S; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas., Lalani SR; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas., Towbin JA; Pediatric Cardiology, University of Tennessee Health Science Center, Memphis, Tennessee., Zender GA; Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, Ohio., Fitzgerald-Butt S; Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, Ohio.; Heart Center, Nationwide Children's Hospital, Columbus, Ohio.; Department of Pediatrics, Ohio State University, Columbus, Ohio., Garg V; Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, Ohio.; Heart Center, Nationwide Children's Hospital, Columbus, Ohio.; Department of Pediatrics, Ohio State University, Columbus, Ohio., Bowman J; Heart Center, Nationwide Children's Hospital, Columbus, Ohio.; Department of Pediatrics, Ohio State University, Columbus, Ohio., Zapata G; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas., Hernandez P; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas., Arrington CB; Division of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah., Furthner D; Children's Hospital, Linz, Austria., Prakash SK; Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas., Bowles NE; Division of Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah., McBride KL; Center for Cardiovascular Research, Nationwide Children's Hospital, Columbus, Ohio.; Heart Center, Nationwide Children's Hospital, Columbus, Ohio.; Department of Pediatrics, Ohio State University, Columbus, Ohio., Belmont JW; Department of Human and Molecular Genetics, Baylor College of Medicine, Houston, Texas.; USDA/ARS/Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2017 Aug; Vol. 173 (8), pp. 2176-2188. Date of Electronic Publication: 2017 Jun 27.
DOI: 10.1002/ajmg.a.38309
Abstrakt: Congenital left-sided cardiac lesions (LSLs) are a significant contributor to the mortality and morbidity of congenital heart disease (CHD). Structural copy number variants (CNVs) have been implicated in LSL without extra-cardiac features; however, non-penetrance and variable expressivity have created uncertainty over the use of CNV analyses in such patients. High-density SNP microarray genotyping data were used to infer large, likely-pathogenic, autosomal CNVs in a cohort of 1,139 probands with LSL and their families. CNVs were molecularly confirmed and the medical records of individual carriers reviewed. The gene content of novel CNVs was then compared with public CNV data from CHD patients. Large CNVs (>1 MB) were observed in 33 probands (∼3%). Six of these were de novo and 14 were not observed in the only available parent sample. Associated cardiac phenotypes spanned a broad spectrum without clear predilection. Candidate CNVs were largely non-recurrent, associated with heterozygous loss of copy number, and overlapped known CHD genomic regions. Novel CNV regions were enriched for cardiac development genes, including seven that have not been previously associated with human CHD. CNV analysis can be a clinically useful and molecularly informative tool in LSLs without obvious extra-cardiac defects, and may identify a clinically relevant genomic disorder in a small but important proportion of these individuals.
(© 2017 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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