{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T12:54:00Z","timestamp":1763643240343,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>This study examined the molecular characterization of a prenatal case with true fetal mosaicism of small supernumerary marker chromosome 16 (sSMC(16)). A 41-year-old female underwent amniocentesis at 19 weeks of gestation due to advanced maternal age. Chromosomal analysis for cultured amniocytes revealed a karyotype of 47,XY,+mar[4]\/46,XY[16]. Spectral karyotyping and metaphase fluorescence in situ hybridization (FISH) demonstrated that the sSMC was derived from chromosome 16 (47,XY,+mar.ish der(16)(D16Z1+)[13\/20]). Confined placental mosaicism was initially suspected because the prenatal ultrasound revealed a normal structure and the pregnancy was uneventful. However, interphase FISH of cord blood performed at 28 weeks of gestation showed 20% mosaicism of trisomy chromosome 16 (nuc ish(D16Z2\u00d73)[40\/200]). Chromosome microarray analysis further demonstrated 55% mosaicism of an 8.02 Mb segmental duplication at the subcentromeric region of 16p12.1p11.1 (arr[GRCh37] 16p12.1p11.1(27021975_35045499)\u00d73[0.55]). The results demonstrated a true fetal mosaicism of sSMC(16) involving chromosome16p12.1p11.1 that is associated with chromosome 16p11.2 duplication syndrome (OMIM #614671). After non-directive genetic counseling, the couple opted for late termination of pregnancy. This case illustrated the use of multiple molecular cytogenetic tools to elucidate the origin and structure of sSMC, which is crucial for prenatal counseling, decision making, and clinical management.<\/jats:p>","DOI":"10.3390\/diagnostics11081457","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:54:41Z","timestamp":1628765681000},"page":"1457","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prenatal Diagnosis of True Fetal Mosaicism with Small Supernumerary Marker Chromosome Derived from Chromosome 16 by Funipuncture and Molecular Cytogenetics Including Chromosome Microarray"],"prefix":"10.3390","volume":"11","author":[{"given":"Tien-Yu","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Ju","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"PhD Programs in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2484-3761","authenticated-orcid":false,"given":"Kim-Seng","family":"Law","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Tung\u2019s Taichung MetroHarbor Hospital, Taichung 43344, Taiwan"},{"name":"Department of Nursing, Jenteh Junior College of Medicine, Nursing and Management, Miaoli 35665, Taiwan"},{"name":"Department of Life Science, National Chung Hsin University, Taichung 40227, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mei-Hui","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-Ping","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong-Jay","family":"Lee","sequence":"additional","affiliation":[{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hsiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Welgene Biotechnology Company, Nangang Business Park, Taipei 11503, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5076-2917","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"PhD Programs in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"},{"name":"Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei 10041, Taiwan"},{"name":"Department of Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan"},{"name":"Department of Molecular Biotechnology, Da-Yeh University, Changhua 51591, Taiwan"},{"name":"Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4925-7101","authenticated-orcid":false,"given":"Gwo-Chin","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Genomic Medicine and Center for Medical Genetics, Changhua Christian Hospital, Changhua 50046, Taiwan"},{"name":"Research Department, Changhua Christian Hospital, Changhua 50006, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000079572","article-title":"Small supernumerary marker chromosomes (sSMC) in humans","volume":"107","author":"Liehr","year":"2004","journal-title":"Cytogenet. Genome Res."},{"key":"ref_2","first-page":"719","article-title":"Frequency of small supernumerary marker chromosomes in prenatal, newborn, developmentally retarded and infertility diagnostics","volume":"19","author":"Liehr","year":"2007","journal-title":"Int. J. Mol. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1002\/pd.1414","article-title":"Prenatal identification of small supernumerary marker chromosomes by FISH in an infant born with mild congenital anomalies","volume":"26","author":"Chen","year":"2006","journal-title":"Prenat. Diagn."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/pd.814","article-title":"Trisomy 13 mosaicism: Study of serial cytogenetic changes in a case from early pregnancy to infancy","volume":"24","author":"Chen","year":"2004","journal-title":"Prenat. Diagn."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/pd.1520","article-title":"Prenatal detection and characterization of a small supernumerary marker. chromosome (sSMC) derived from chromosome 22 with apparently normal phynoetype","volume":"26","author":"Lin","year":"2006","journal-title":"Prenat. Diagn."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1002\/ajmg.a.32878","article-title":"Small supernumerary marker chromosome originating from chromosome 10 associated with an apparently normal phenotype","volume":"149","author":"Sung","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.tjog.2017.06.004","article-title":"Prenatal diagnosis and molecular cytogenetic. characterization of mosaicism for a small supernumerary marker chromosome derived from chromosome 21q11.2q21.1 and a literature review","volume":"56","author":"Chen","year":"2017","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s13039-019-0425-5","article-title":"Molecular cytogenetic identification of small supernumerary marker chromosome using chromosome microarray analysis","volume":"12","author":"Xue","year":"2019","journal-title":"Mol. Cytogenet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.tjog.2021.01.014","article-title":"Low-level mosaicism for trisomy 16 at amniocentesis in a pregnancy associated with intrauterine growth restriction and a favorable outcome","volume":"60","author":"Chen","year":"2021","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/nature03187","article-title":"The sequence and analysis of duplication-rich human chromosome 16","volume":"432","author":"Martin","year":"2004","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1101\/gr.228718.117","article-title":"Detection and analysis of ancient segmental duplications in mammalian genomes","volume":"28","author":"Pu","year":"2018","journal-title":"Genome Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/nature19075","article-title":"Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility","volume":"536","author":"Nuttle","year":"2016","journal-title":"Nature"},{"key":"ref_14","first-page":"378","article-title":"Trisomy 16, cause of first trimester abortion","volume":"51","author":"Khan","year":"2001","journal-title":"J. Pak. Med. Assoc."},{"key":"ref_15","first-page":"111","article-title":"Chromosome abnormalities identified in 457 spontaneous abortions and their histopathological findings","volume":"31","author":"Yakut","year":"2015","journal-title":"Turk Patoloji Derg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104027","DOI":"10.1016\/j.ejmg.2020.104027","article-title":"Clinical and genetic findings in Hungarian pediatric patients carrying chromosome 16p copy number variants and a review of the literature","volume":"63","author":"Lengyel","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1136\/jmg.2009.069369","article-title":"Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder","volume":"47","author":"Fernandez","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/ng.474","article-title":"Microduplications of 16p11.2 are associated with schizophrenia","volume":"41","author":"McCarthy","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/mp.2016.84","article-title":"Chromosomal contacts connect loci associated with autism, BMI and head circumference phenotypes","volume":"22","author":"Loviglio","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13229-018-0239-z","article-title":"Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model","volume":"9","author":"Haslinger","year":"2018","journal-title":"Mol. Autism."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nature11091","article-title":"KCTD13 is a major driver of mirrored neuroanatomical phenotypes of the 16p11.2 copy number variant","volume":"485","author":"Golzio","year":"2012","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nature24470","article-title":"Kctd13 deletion reduces synaptic transmission via increased RhoA","volume":"551","author":"Escamilla","year":"2017","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.eplepsyres.2019.02.008","article-title":"Increased expression of DOC2A in human and rat temporal lobe epilepsy","volume":"151","author":"Hu","year":"2019","journal-title":"Epilepsy Res."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/8\/1457\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:44:39Z","timestamp":1760165079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/8\/1457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":24,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["diagnostics11081457"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11081457","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2021,8,12]]}}}