@Article{chd.2022.021580,
AUTHOR = {Jun Sung Park, Go Hun Seo, Yunha Choi, Soojin Hwang, Minji Kang, Hyo-Sang Do, Young-Hwue Kim, Jeong Jin Yu, Ellen Ai-Rhan Kim, Euiseok Jung, Byong Sop Lee, Jae Suk Baek, Beom Hee Lee,6},
TITLE = {Factors Affecting the Genetic Diagnostic Rate in Congenital Heart Disease},
JOURNAL = {Congenital Heart Disease},
VOLUME = {17},
YEAR = {2022},
NUMBER = {6},
PAGES = {653--673},
URL = {http://www.techscience.com/chd/v17n6/50102},
ISSN = {1747-0803},
ABSTRACT = {Background: Over 400 genes contribute to the development of congenital heart disease (CHD). Additionally,
multisystemic manifestations accompanying syndromic CHD pose a higher risk of genetic diseases. This study
investigated the diagnostic yield of whole-exome sequencing (WES) in patients with sporadic syndromic CHD
and the phenotypic factors affecting the genetic diagnostic rate. Methods: Sixty-four patients with sporadic syndromic CHD aged <18 years underwent WES between May 2018 and December 2020 in a single tertiary center,
and the association between genetic testing data and extracardiac phenotypes was analyzed. Results: Extracardiac
phenotypes were measured as 3.66 ± 3.05 (standard deviation, interquartile range: 2–5) items per patient. WES
detected diagnostic variants in 19 (29.7%) patients: seven (36.8%), seven (36.8%), and five (26.3%) with pathogenic variants, likely pathogenic variants, and variants of unknown significance, respectively. Post-diagnosis surveillance identified the extracardiac phenotype in 54.5% (6/11) of patients. De novo variants accounted for 76.2%
(15/19) of variants and autosomal dominant inheritance for 94.7% (18/19). Most diseases were ultra-rare. No significant differences were noted in cardiac and extracardiac phenotypes, single or combined (all P > 0.05), between
the groups with and without a diagnostic variant. However, patients with ≥3 extracardiac phenotypes had a significantly higher likelihood of having a diagnostic variant than those with ≤2 (38.3% vs. 5.9%, odds ratio = 9.93,
95% confidence interval = 1.21–81.44, P = 0.013). Conclusions: The number of extracardiac phenotypes is important in predicting the possibility of genetic diagnosis. Physicians will be able to select patients with a high probability of genetic diagnosis and provide appropriate genetic counseling based on the results of this study.},
DOI = {10.32604/chd.2022.021580}
}