Author:
Li Ping,Chen Weicheng,Li Mengru,Zhao Zhengshan,Feng Zhiyu,Gao Han,Suo Meijiao,Xu Ziqing,Tian Guixiang,Wu Feizhen,Wei Sheng,Huang Guoying
Abstract
Abstract
Background
Syndromic congenital heart disease (CHD) is among the most severe conditions in the pediatric population. Copy number variant (CNV) is an important cause of syndromic CHD, but few studies focused on CNVs related to these patients in China. The present study aimed to identify pathogenic CNVs associated with syndromic CHD in the Chinese population.
Methods
A total of 109 sporadic patients with syndromic CHD were applied chromosomal microarray analysis (CMA). Phenotype spectrum of pathogenic or likely pathogenic CNVs was analyzed. CHD-related genes were prioritized from genes within pathogenic or likely pathogenic CNVs by VarElect, OVA, AMELIE, and ToppGene.
Results
Using CMA, we identified 43 candidate CNVs in 37/109 patients. After filtering CNVs present in the general population, 29 pathogenic/likely pathogenic CNVs in 24 patients were identified. The diagnostic yield of CMA for pathogenic/likely pathogenic CNVs was 23.1% (24/104), excluding 5 cases with aneuploidies or gross chromosomal aberrations. The overlapping analysis of CHD-related gene lists from different prioritization tools highlighted 16 CHD candidate genes.
Conclusion
As the first study focused on CNVs in syndromic CHD from the Chinese population, this study reveals the importance of CMA in exploring the genetic etiology of syndromic CHD and expands our understanding of these complex diseases. The bioinformatic analysis of candidate genes suggests several CHD-related genes for further functional research.
Funder
National Natural Science Foundation of China
National Key Research and Development Program of China
Shanghai Basic Research Project of Science and Technology Innovation Action Plan
Chinese Academy of Medical Sciences Research Unit
Shanghai Natural Science Foundation of Science and Technology Innovation Action Plan
Publisher
Springer Science and Business Media LLC
Subject
Drug Discovery,Genetics,Molecular Biology,Molecular Medicine
Reference62 articles.
1. Wilde AAM, Semsarian C, Márquez MF, Sepehri Shamloo A, Ackerman MJ, Ashley EA, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases. Heart Rhythm. 2022;19(7):e1–e60.
2. Gonzalez JH, Shirali GS, Atz AM, Taylor SN, Forbus GA, Zyblewski SC, et al. Universal screening for extracardiac abnormalities in neonates with congenital heart disease. Pediatr Cardiol. 2009;30(3):269–73.
3. Itsara A, Cooper GM, Baker C, Girirajan S, Li J, Absher D, et al. Population analysis of large copy number variants and hotspots of human genetic disease. Am J Hum Genet. 2009;84(2):148–61.
4. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, et al. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367(23):2175–84.
5. Kearney HM, Thorland EC, Brown KK, Quintero-Rivera F, South ST. American College of Medical Genetics standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants. Genet Med Off J Am Coll Med Genet. 2011;13(7):680–5.