@article{73c423adfd2e4e3388b9b53c14556add,
title = "Prevalence and Spectrum of Congenital Heart Disease in Individuals With Distal Chromosome 22q11.22–23 Deletions",
abstract = "This study is aimed at determining the spectrum of congenital heart disease associated with distal 22q11.22–23 deletions flanked by low copy repeats, LCR22 D–H. We analyzed cardiology findings in 128 unrelated individuals with distal LCR22 D–H deletions. A total of 62 were newly described and 66 were derived from previous reports. We found that deletions which included LCR22-D as the proximal endpoint were the most prevalent in the cohort (104/128, 81.3\%). Clinically relevant congenital heart disease was identified in 48 individuals (37.5\%, 95\% CI 29\%–46\%), which is lower than the prevalence reported for typical, proximal LCR22 A–D deletions (p = 3.7E-4), especially for conotruncal defects (13/128, 10.2\%; p = 7.1E-13). Mild to moderate CHD predominated, including ventricular septal defects (22/128), bicuspid aortic valve (9/128) and mild cardiomyopathy (3/128). Persistent truncus arteriosus was the most prevalent (n = 8/13) conotruncal heart defect, but other anomalies also occurred in singleton cases. These findings support the need for cardiac evaluation in all individuals with distal 22q11.22–23 deletions, increased use of clinical genetic testing in syndromic individuals with these findings, and molecular studies in model systems. The results demonstrate that reduced gene dosage of distal 22q11.21–23, particularly within the D–E region including MAPK1 and HIC2 convey risk for CHD.",
keywords = "22q11.2 distal deletion, chromosome abnormalities, chromosome deletion, congenital heart disease, heart defects-congenital",
author = "Nelson, \{Tanner J.\} and McGinn, \{Daniel E.\} and Crowley, \{T. Blaine\} and Lydia Rockart and Audrey Green and Victoria Giunta and Oanh Tran and Daniella Miller and Jeroen Breckpot and Ann Swillen and Digilio, \{M. Cristina\} and Marta Unolt and Carolina Putotto and Federica Pulvirenti and Bruno Marino and Emanuel, \{Beverly S.\} and Zackai, \{Elaine H.\} and Zhang, \{Zhengdong D.\} and Elizabeth Goldmuntz and Erik Boot and Bassett, \{Anne S.\} and Morrow, \{Bernice E.\} and McDonald-McGinn, \{Donna M.\}",
note = "Funding Information: This work was supported by the National Institutes of Health (P01HD070454, R01HL157157, R01GM125757, R01GM125757\textbackslash{}u201303, U01MH101720), and the Canadian Institutes of Health Research (MOP\textbackslash{}u2010313331, MOP\textbackslash{}u2010111238) and from the Inaugural Dalglish Chair in 22q11.2 Deletion Syndrome. Funding Information: We owe an enormous debt of gratitude to all individuals and families who contributed to this investigation. This work was supported by NIH grants P01HD070454, R01HL157157, R01GM125757, R01GM125757\textbackslash{}u201003, and U01MH101720, and in part by the Canadian Institutes of Health Research (CIHR) [MOP\textbackslash{}u2010313331 and MOP\textbackslash{}u2010111238] and from the Inaugural Dalglish Chair in 22q11.2 Deletion Syndrome at the University of Toronto and University Health Network to A.S.B. AI was not used in the writing process. Publisher Copyright: {\textcopyright} 2025 The Author(s). Clinical Genetics published by John Wiley \& Sons Ltd.",
year = "2025",
month = jan,
day = "1",
doi = "10.1111/cge.70118",
language = "English",
journal = "Clinical Genetics",
issn = "0009-9163",
publisher = "Wiley-Blackwell",
}