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Project of Guangzhou Science and Technology","award":["2017A030313460"],"award-info":[{"award-number":["2017A030313460"]}]},{"name":"The Project of Guangzhou Science and Technology","award":["20221A011038"],"award-info":[{"award-number":["20221A011038"]}]},{"name":"The Project of Guangzhou Science and Technology","award":["202102020191"],"award-info":[{"award-number":["202102020191"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>(1) Objective: To investigate the prenatal diagnosis and genetic counseling for 16p11.2 microdeletion syndrome and to evaluate its pregnancy outcome. (2) Methods: This study included 4968 pregnant women who selected invasive prenatal diagnoses from 1 January 2017 to 1 August 2022. These 4698 pregnancies underwent chromosomal microarray analysis (CMA), data on 81 fetuses diagnosed with 16p11.2 microdeletion syndrome based on prenatal ultrasound features and genetic test results were recorded, and their pregnancy outcome was evaluated. (3) Results: 1.63% of fetuses (81\/4968) were diagnosed with 16p11.2 microdeletion syndrome. Among these, there were skeletal malformations in 48.15% of the 81 fetuses, cardiovascular malformations in 30.86%, central nervous system malformations (CNS) in 11.11%, digestive system structural abnormalities in 6.17%, and isolated ultrasonography markers in 3.70%. (4) Conclusions: 16p11.2 microdeletion syndrome can display various systemic ultrasound abnormalities in the perinatal period but vertebral malformations are the most common. Our study is the first to report that TBX1 and CJA5 are associated with 16p11.2 microdeletion syndrome, expanding the disease spectrum of 16p11.2 microdeletion syndrome. In our study, the ventricular septal defect is the main feature of cardiac structural abnormalities caused by 16p11.2 microdeletion syndrome. In addition, our study highlights the use of CMA in 16p11.2 microdeletion syndrome, analyzed their genetic results, and evaluated the follow-up prognosis, which can be useful for prenatal diagnosis and genetic counseling.<\/jats:p>","DOI":"10.3390\/genes13122315","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T02:20:31Z","timestamp":1670552431000},"page":"2315","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Prenatal Diagnosis of Chromosome 16p11.2 Microdeletion"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5405-1255","authenticated-orcid":false,"given":"You","family":"Wang","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"},{"name":"Department of Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-5065","authenticated-orcid":false,"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Fu","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4011-9199","authenticated-orcid":false,"given":"Ken","family":"Cheng","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"},{"name":"School of Medicine, South China University of Technology, Guangzhou 510641, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuxia","family":"Yu","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8929-7805","authenticated-orcid":false,"given":"Ruibin","family":"Huang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingying","family":"Lei","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongzhi","family":"Li","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Liao","sequence":"additional","affiliation":[{"name":"The First School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s11689-009-9037-4","article-title":"Speech Delays and Behavioral Problems Are the Predominant Features in Individuals with Developmental Delays and 16p11.2 Microdeletions and Microduplications","volume":"2","author":"Rosenfeld","year":"2010","journal-title":"J. Neurodev. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1093\/hmg\/ddm376","article-title":"Recurrent 16p11.2 Microdeletions in Autism","volume":"17","author":"Kumar","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nature10406","article-title":"Mirror Extreme Bmi Phenotypes Associated with Gene Dosage at the Chromosome 16p11.2 Locus","volume":"478","author":"Jacquemont","year":"2011","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1056\/NEJMoa075974","article-title":"Association between Microdeletion and Microduplication at 16p11.2 and Autism","volume":"358","author":"Weiss","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1002\/ajmg.b.31147","article-title":"Intra-Family Phenotypic Heterogeneity of 16p11.2 Deletion Carriers in a Three-Generation Chinese Family","volume":"156","author":"Shen","year":"2011","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_6","first-page":"1066","article-title":"The Atypical 16p11.2 Deletion: A Not So Atypical Microdeletion Syndrome?","volume":"155a","author":"Maas","year":"2011","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/s41380-018-0118-1","article-title":"Dose Response of the 16p11.2 Distal Copy Number Variant on Intracranial Volume and Basal Ganglia","volume":"25","author":"Doan","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1002\/pd.5245","article-title":"Intrauterine Phenotypic Features Associated with 16p11.2 Recurrent Microdeletions","volume":"38","author":"Lin","year":"2018","journal-title":"Prenat. Diagn."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1097\/GIM.0b013e3182217a3a","article-title":"American College of Medical Genetics Standards and Guidelines for Interpretation and Reporting of Postnatal Constitutional Copy Number Variants","volume":"13","author":"Kearney","year":"2011","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1136\/jmg.2009.073015","article-title":"Recurrent Reciprocal 16p11.2 Rearrangements Associated with Global Developmental Delay, Behavioural Problems, Dysmorphism, Epilepsy, and Abnormal Head Size","volume":"47","author":"Shinawi","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1136\/jmedgenet-2017-105013","article-title":"Practice Guideline: Joint Ccmg-Sogc Recommendations for the Use of Chromosomal Microarray Analysis for Prenatal Diagnosis and Assessment of Fetal Loss in Canada","volume":"55","author":"Armour","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Committee on Genetics, and Society for Maternal\u2013Fetal Medicine (2016). Committee Opinion No.682: Microarrays and Next-Generation Sequencing Technology: The Use of Advanced Genetic Diagnostic Tools in Obstetrics and Gynecology. Obstet. Gynecol., 128, e262\u2013e268.","DOI":"10.1097\/AOG.0000000000001817"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.biopsych.2014.04.021","article-title":"The Cognitive and Behavioral Phenotype of the 16p11.2 Deletion in a Clinically Ascertained Population","volume":"77","author":"Hanson","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_14","first-page":"1118","article-title":"Scoliosis and Vertebral Anomalies: Additional Abnormal Phenotypes Associated with Chromosome 16p11.2 Rearrangement","volume":"164a","author":"Khanna","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1097\/BRS.0b013e3181bc963c","article-title":"The Association Analysis of Tbx6 Polymorphism with Susceptibility to Congenital Scoliosis in a Chinese Han Population","volume":"35","author":"Fei","year":"2010","journal-title":"Spine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1136\/jmedgenet-2019-106333","article-title":"Increased Tbx6 Gene Dosages Induce Congenital Cervical Vertebral Malformations in Humans and Mice","volume":"57","author":"Ren","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1034\/j.1399-0004.2001.600602.x","article-title":"When Body Segmentation Goes Wrong","volume":"60","author":"Kusumi","year":"2001","journal-title":"Clin. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1056\/NEJMoa1406829","article-title":"Tbx6 Null Variants and a Common Hypomorphic Allele in Congenital Scoliosis","volume":"372","author":"Wu","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1002\/ajmg.a.31837","article-title":"A Novel Microdeletion at 16p11.2 Harbors Candidate Genes for Aortic Valve Development, Seizure Disorder, and Mild Mental Retardation","volume":"143a","author":"Ghebranious","year":"2007","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/s13353-011-0063-z","article-title":"Mental Retardation and Autism Associated with Recurrent 16p11.2 Microdeletion: Incomplete Penetrance and Variable Expressivity","volume":"52","author":"Patsalis","year":"2011","journal-title":"J. Appl. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1177\/0883073815602066","article-title":"The Influence of Microdeletions and Microduplications of 16p11.2 on Global Transcription Profiles","volume":"30","author":"Kusenda","year":"2015","journal-title":"J. Child. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ejhg.2013.141","article-title":"An Unusual Clinical Severity of 16p11.2 Deletion Syndrome Caused by Unmasked Recessive Mutation of Cln3","volume":"22","author":"Greze","year":"2014","journal-title":"Eur. J. Hum. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2315\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:36:43Z","timestamp":1760146603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/12\/2315"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,8]]},"references-count":22,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["genes13122315"],"URL":"https:\/\/doi.org\/10.3390\/genes13122315","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,8]]}}}