{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:03:26Z","timestamp":1760148206334,"version":"build-2065373602"},"reference-count":73,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82071504","81930104","82101545","2021ZD0200600","2021ZD0202000","2021ZD0203000","2021-I2M-1-020","2021-I2M-1-052"],"award-info":[{"award-number":["82071504","81930104","82101545","2021ZD0200600","2021ZD0202000","2021ZD0203000","2021-I2M-1-020","2021-I2M-1-052"]}]},{"name":"STI2030-Major Projects","award":["82071504","81930104","82101545","2021ZD0200600","2021ZD0202000","2021ZD0203000","2021-I2M-1-020","2021-I2M-1-052"],"award-info":[{"award-number":["82071504","81930104","82101545","2021ZD0200600","2021ZD0202000","2021ZD0203000","2021-I2M-1-020","2021-I2M-1-052"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["82071504","81930104","82101545","2021ZD0200600","2021ZD0202000","2021ZD0203000","2021-I2M-1-020","2021-I2M-1-052"],"award-info":[{"award-number":["82071504","81930104","82101545","2021ZD0200600","2021ZD0202000","2021ZD0203000","2021-I2M-1-020","2021-I2M-1-052"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Microtia is a congenital malformation characterized by a small, abnormally shaped auricle (pinna) ranging in severity. Congenital heart defect (CHD) is one of the comorbid anomalies with microtia. However, the genetic basis of the co-existence of microtia and CHD remains unclear. Copy number variations (CNVs) of 22q11.2 contribute significantly to microtia and CHD, respectively, thus suggesting a possible shared genetic cause embedded in this genomic region. In this study, 19 sporadic patients with microtia and CHD, as well as a nuclear family, were enrolled for genetic screening of single nucleotide variations (SNVs) and CNVs in 22q11.2 by target capture sequencing. We detected a total of 105 potential deleterious variations, which were enriched in ear- or heart-development-related genes, including TBX1 and DGCR8. The gene burden analysis also suggested that these genes carry more deleterious mutations in the patients, as well as several other genes associated with cardiac development, such as CLTCL1. Additionally, a microduplication harboring SUSD2 was validated in an independent cohort. This study provides new insights into the underlying mechanisms for the comorbidity of microtia and CHD focusing on chromosome 22q11.2, and suggests that a combination of genetic variations, including SNVs and CNVs, may play a crucial role instead of single gene mutation.<\/jats:p>","DOI":"10.3390\/genes14040879","type":"journal-article","created":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T03:49:29Z","timestamp":1681098569000},"page":"879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Screening of Targeted Region on the Chromosome 22q11.2 in Patients with Microtia and Congenital Heart Defect"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4405-0889","authenticated-orcid":false,"given":"Caiyun","family":"Zhu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"},{"name":"Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100144, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100144, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Wei","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"},{"name":"Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahang","family":"Ju","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"},{"name":"Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1985-3420","authenticated-orcid":false,"given":"Nuo","family":"Si","sequence":"additional","affiliation":[{"name":"Research Center, Plastic Surgery Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100144, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China"},{"name":"Neuroscience Center, Chinese Academy of Medical Sciences, Beijing 100005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1136\/jmg.2008.062158","article-title":"Genetics of microtia and associated syndromes","volume":"46","author":"Alasti","year":"2009","journal-title":"J. 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