{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:10:07Z","timestamp":1792714207002,"version":"4.5.0"},"reference-count":25,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The copy number variation (CNV) of 15q11.2, an emerging and common condition observed during prenatal counseling, is encompassed by four highly conserved and non-imprinted genes\u2014TUBGCP5, CYFIP1, NIPA1, and NIPA2\u2014which are reportedly related to developmental delays or general behavioral problems. We retrospectively analyzed 1337 samples from genetic amniocentesis for fetal CNV using microarray-based comparative genomic hybridization analysis between January 2014 and December 2019. 15q11.2 CNV showed a prevalence of 1.5% (21\/1337). Separately, 0.7% was noted for 15q11.2 BP1\u2013BP2 microdeletion and 0.8% for 15q11.2 microduplication. Compared to the normal array group, the 15q11.2 BP1\u2013BP2 microdeletion group had more cases of neonatal intensive care unit transfer, an Apgar score of &lt;7 at 1 min, and neonatal death. Additionally, the group was symptomatic with developmental delays and had more infantile deaths related to congenital heart disease (CHD). Our study makes a novel contribution to the literature by exploring the differences in the adverse perinatal outcomes and early life conditions between the 15q11.2 CNV and normal array groups. Parent-origin gender-based differences may help in the prognosis of the fetal phenotype; development levels should be followed up in the long term and echocardiography should be offered prenatally and postnatally for the prevention of a delayed diagnosis of CHD.<\/jats:p>","DOI":"10.3390\/genes12101480","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T09:59:15Z","timestamp":1632391155000},"page":"1480","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Adverse Perinatal and Early Life Outcomes following 15q11.2 CNV Diagnosis"],"prefix":"10.3390","volume":"12","author":[{"given":"Fu-Chieh","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 114, Taiwan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3931-7297","authenticated-orcid":false,"given":"Steven W.","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 114, Taiwan, China"},{"name":"College of Medicine, Chang Gung University, Taoyuan 330, Taiwan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 333, Taiwan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang-Ming","family":"Lo","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 114, Taiwan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenn-Jeih","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 114, Taiwan, China"},{"name":"College of Medicine, Chang Gung University, Taoyuan 330, Taiwan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2354-7060","authenticated-orcid":false,"given":"Tai-Ho","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Taipei Chang Gung Memorial Hospital, Taipei 114, Taiwan, China"},{"name":"College of Medicine, Chang Gung University, Taoyuan 330, Taiwan, China"},{"name":"Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/s00439-011-0970-4","article-title":"Microdeletion\/microduplication of proximal 15q11.2 between BP1 and BP2: A susceptibility region for neurological dysfunction including developmental and language delay","volume":"130","author":"Burnside","year":"2011","journal-title":"Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4068","DOI":"10.3390\/ijms16024068","article-title":"The 15q11.2 BP1-BP2 microdeletion syndrome: A review","volume":"16","author":"Cox","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1002\/ajmg.a.37134","article-title":"Deletion of 15q11.2(BP1-BP2) region: Further evidence for lack of phenotypic specificity in a pediatric population","volume":"167","author":"Hashemi","year":"2015","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/jir.12382","article-title":"Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder","volume":"61","author":"Butler","year":"2017","journal-title":"J. Intellect. Disabil. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1002\/ajmg.b.32480","article-title":"Recurrent 15q11.2 BP1-BP2 microdeletions and microduplications in the etiology of neurodevelopmental disorders","volume":"171","author":"Picinelli","year":"2016","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rafi, S.K., and Butler, M.G. (2020). The 15q11.2 BP1-BP2 Microdeletion (Burnside-Butler) Syndrome: In Silico Analyses of the Four Coding Genes Reveal Functional Associations with Neurodevelopmental Phenotypes. Int. J. Mol. Sci., 21.","DOI":"10.37247\/PAMOLSCS.1.2020.17"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1002\/ajmg.a.36554","article-title":"Phenotypic features in patients with 15q11.2(BP1-BP2) deletion: Further delineation of an emerging syndrome","volume":"164A","author":"Cafferkey","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejmg.2009.03.010","article-title":"Nine patients with a microdeletion 15q11.2 between breakpoints 1 and 2 of the Prader-Willi critical region, possibly associated with behavioural disturbances","volume":"52","author":"Doornbos","year":"2009","journal-title":"Eur. J. Med. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/gim.2012.164","article-title":"Estimates of penetrance for recurrent pathogenic copy-number variations","volume":"15","author":"Rosenfeld","year":"2013","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"041","DOI":"10.3233\/PGE-14082","article-title":"Further phenotypic expansion of 15q11.2 BP1-BP2 microdeletion (Burnside-Butler) syndrome","volume":"03","author":"Jerkovich","year":"2015","journal-title":"J. Pediatric Genet."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ho, K.S., Wassman, E.R., Baxter, A.L., Hensel, C.H., Martin, M.M., Prasad, A., Twede, H., Vanzo, R.J., and Butler, M.G. (2016). Chromosomal Microarray Analysis of Consecutive Individuals with Autism Spectrum Disorders Using an Ultra-High Resolution Chromosomal Microarray Optimized for Neurodevelopmental Disorders. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122070"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1136\/jmedgenet-2018-105879","article-title":"Estimating the effect size of the 15Q11.2 BP1-BP2 deletion and its contribution to neurodevelopmental symptoms: Recommendations for practice","volume":"56","author":"Douard","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_13","unstructured":"Wang, T.M. (2003). The Comprehensive Developmental Inventory for Infants and Toddlers\u2014Manual."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nebel, R.A., Zhao, D., Pedrosa, E., Kirschen, J., Lachman, H.M., Zheng, D., and Abrahams, B.S. (2016). Reduced CYFIP1 in Human Neural Progenitors Results in Dysregulation of Schizophrenia and Epilepsy Gene Networks. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148039"},{"key":"ref_15","first-page":"2846","article-title":"Genetic counseling for susceptibility loci and neurodevelopmental disorders: The del15q11.2 as an example","volume":"161A","author":"Brison","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1109","DOI":"10.1038\/tp.2017.77","article-title":"15q11.2 CNV affects cognitive, structural and functional correlates of dyslexia and dyscalculia","volume":"7","author":"Ulfarsson","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.ejmg.2010.12.008","article-title":"15q11.2 microdeletion\u2014seven new patients with delayed development and\/or behavioural problems","volume":"54","author":"Rustad","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xie, H., Zhang, Y., Zhang, P., Wang, J., Wu, Y., Wu, X., Netoff, T., and Jiang, Y. (2014). Functional study of NIPA2 mutations identified from the patients with childhood absence epilepsy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0109749"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1086\/378817","article-title":"NIPA1 gene mutations cause autosomal dominant hereditary spastic paraplegia (SPG6)","volume":"73","author":"Rainier","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.ajhg.2012.08.003","article-title":"Contribution of global rare copy-number variants to the risk of sporadic congenital heart disease","volume":"91","author":"Soemedi","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/s41431-020-0626-8","article-title":"Association of congenital cardiovascular malformation and neuropsychiatric phenotypes with 15q11.2 (BP1-BP2) deletion in the UK Biobank","volume":"28","author":"Williams","year":"2020","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Davis, K.W., Serrano, M., Loddo, S., Robinson, C., Alesi, V., Dallapiccola, B., Novelli, A., and Butler, M.G. (2019). Parent-of-Origin Effects in 15q11.2 BP1-BP2 Microdeletion (Burnside-Butler) Syndrome. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20061459"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1159\/000477226","article-title":"Major Contribution of Genomic Copy Number Variation in Syndromic Congenital Heart Disease: The Use of MLPA as the First Genetic Test","volume":"8","author":"Monteiro","year":"2017","journal-title":"Mol. Syndromol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.tjog.2019.07.014","article-title":"Prenatally diagnosed de novo segmental amplification or deletion by microarray-based comparative genomic hybridization: A retrospective study","volume":"58","author":"Peng","year":"2019","journal-title":"Taiwan J. Obstet. Gynecol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ejmg.2015.01.002","article-title":"15q11.2 microdeletion (BP1-BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: A series of 52 patients","volume":"58","author":"Vanlerberghe","year":"2015","journal-title":"Eur. J. Med. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/10\/1480\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:03:49Z","timestamp":1760166229000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/10\/1480"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,23]]},"references-count":25,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["genes12101480"],"URL":"https:\/\/doi.org\/10.3390\/genes12101480","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,23]]}}}