{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T03:12:08Z","timestamp":1777173128652,"version":"3.51.4"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Microcephaly is common in patients with neuropsychiatric problems, and it is usually closely related to genetic causes. However, studies on chromosomal abnormalities and single-gene disorders associated with fetal microcephaly are limited.<\/jats:p><jats:p><jats:bold>Objective:<\/jats:bold> We investigated the cytogenetic and monogenic risks of fetal microcephaly and evaluated their pregnancy outcomes.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We performed a clinical evaluation, high-resolution chromosomal microarray analysis (CMA), and trio exome sequencing (ES) on 224 fetuses with prenatal microcephaly and closely followed the pregnancy outcome and prognosis.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Among 224 cases of prenatal fetal microcephaly, the diagnosis rate was 3.74% (7\/187) for CMA and 19.14% (31\/162) for trio-ES. Exome sequencing identified 31 pathogenic or likely pathogenic (P\/LP) single nucleotide variants (SNVs) in 25 genes associated with fetal structural abnormalities in 37 microcephaly fetuses; 19 (61.29%) of which occurred <jats:italic>de novo<\/jats:italic>. Variants of unknown significance (VUS) was found in 33\/162 (20.3%) fetuses. The gene variant involved included the single gene <jats:italic>MPCH 2<\/jats:italic> and <jats:italic>MPCH 11<\/jats:italic>, which is associated with human microcephaly, and <jats:italic>HDAC8, TUBGCP6, NIPBL, FANCI, PDHA1, UBE3A, CASK, TUBB2A, PEX1, PPFIBP1, KNL1, SLC26A4, SKIV2L, COL1A2, EBP, ANKRD11, MYO18B, OSGEP, ZEB2, TRIO, CLCN5, CASK,<\/jats:italic> and <jats:italic>LAGE3<\/jats:italic>. The live birth rate of fetal microcephaly in the syndromic microcephaly group was significantly higher than that in the primary microcephaly group [62.9% (117\/186) vs 31.56% (12\/38), <jats:italic>p<\/jats:italic> = 0.000].<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> We conducted a prenatal study by conducting CMA and ES for the genetic analysis of fetal microcephaly cases. CMA and ES had a high diagnostic rate for the genetic causes of fetal microcephaly cases. In this study, we also identified 14 novel variants, which expanded the disease spectrum of microcephaly-related genes.<\/jats:p>","DOI":"10.3389\/fgene.2023.1112153","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T05:14:37Z","timestamp":1683609277000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetic diagnosis of fetal microcephaly at a single tertiary center in China"],"prefix":"10.3389","volume":"14","author":[{"given":"You","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingying","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunling","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruibin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuxia","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lushan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongzhi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1038\/s41436-021-01121-0","article-title":"High diagnosis rate for nonimmune hydrops fetalis with prenatal clinical exome from the Hydrops-Yielding Diagnostic Results of Prenatal Sequencing (HYDROPS) Study","volume":"23","author":"Al-Kouatly","year":"2021","journal-title":"Genet. 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