Array Comparative Genomic Hybridization as a Diagnostic Tool for Syndromic Heart Defects

1q21.1 Microduplication expression in adults

“…1,2,[5][6][7][8][9][10][11][12] We also examined primary articles and reviews of CNVs in autism, 13 schizophrenia, 14 mental retardation, 15 and congenital heart disease 16 for references to studies reporting subjects with 1q21.1 duplications. [17][18][19][20] Other citations involving 1q21.1 duplication cases were also assessed. [21][22][23][24][25][26][27][28][29][30][31][32][33][34] Cases of 1q21.1 duplication in GeneReviews (http://www.ncbi.nlm.…”

“…3,35 We systematically reviewed 28 primary reports identified and their accompanying supplemental materials to identify unique individuals and abstract as much information as possible on each subject. 1,2,[5][6][7][8][9][10][11][12][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Any subjects with 1q21.1 duplications that were not 1.0-5.0 Mb (Figure 1) in size were excluded, 12,31 allowing us to include atypical variants that were larger or smaller than the standard duplication classes used in our analyses. We documented the ascertainment criteria, country of origin, authors, and the demographic, clinical, and genotypic characteristics of subjects in different studies, and used these variables to attempt to identify duplicate cases reported in two or more papers.…”

“…Four studies were excluded because the sources of subjects overlapped with those of other reports and/or the origin of cases was not specified. 17,18,32,34 We compiled data for 107 subjects from the remaining 22 studies 1,2,[5][6][7][8][9][10][11][19][20][21][22][23][24][25][26][27][28][29][30]33 for the main analyses in this report.…”

Genetics and Genetic Testing in Congenital Heart Disease

“…In addition, there is evidence that genetic testing is frequently underutilized in infants with CHD 55,56 . Nevertheless, the importance of genetic evaluation of patients with CHD has been emphasized in a position statement from the American Heart Association 57 , which cites four specific reasons to pursue testing:…”

“…These developments are significant: an ever-growing body of studies indicate that pathogenic CNVs are a major cause of CHDs, occurring in 3-25% of patients with extra-cardiac abnormalities and in 3-10% of patients with isolated heart defects (reviewed in Lander et al 9 ). In practice, the relatively limited resolutions of karyotyping and FISH have rendered them insufficient to detect a genetic cause in the majority of patients with CHDs of uncertain etiology 55 and in nearly half of all patients with syndromic CHD 61 . Therefore, use of CMA as a higher fidelity option for firstline CHD genetic testing has been recommended, particularly when extra-cardiac features are present and a suspected diagnosis is lacking 61 .…”