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Cases with abnormal chromosomal microarray analysis (CMA) and TORCH results were excluded.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty\u2010one fetuses with isolated and severe FGR and negative CMA results underwent Trio\u2010WES. Of all patients, eight (15.7%) were diagnosed with FGR at its early onset (&lt;32\u2009weeks) and showed pathogenic or likely pathogenic variants involving Nipped\u2010B\u2010like protein gene (<jats:italic>NIPBL<\/jats:italic>) (<jats:italic>n<\/jats:italic>\u00a0=\u20093), fibroblast growth factor receptor 3 (<jats:italic>n<\/jats:italic>\u00a0=\u20091), pyruvate dehydrogenase E1 subunit alpha 1 (<jats:italic>n<\/jats:italic>\u00a0=\u20091), collagen, type I, alpha 1 (<jats:italic>n<\/jats:italic>\u00a0=\u20091), superkiller viralicidic activity 2\u2010like (<jats:italic>n<\/jats:italic>\u00a0=\u20091), and chloride voltage\u2010gated channel (<jats:italic>CLCN5<\/jats:italic>) (<jats:italic>n<\/jats:italic>\u00a0=\u20091). De novo\u2013generated variants were identified in five fetuses, of which two were novel, including c.6983C&gt;A (p. Thr2328Lys) in NIPBL and c.934\u20101G&gt;T in CLCN5. Genetic disorders involved Cornelia de Lange syndrome and metabolic and skeletal genetic diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The present study indicates that Trio\u2010WES can improve effectivity of prenatal diagnoses for isolated and severe FGR in cases with normal CMA results, aiding prenatal genetic counseling and pregnancy management for FGR fetuses.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ijgo.14620","type":"journal-article","created":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T14:39:22Z","timestamp":1670683162000},"page":"1004-1011","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Genetic causes of isolated and severe fetal growth restriction in normal chromosomal microarray 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruibin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnostic center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnostic center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxia","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnostic center, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Prenatal Diagnostic center, Guangzhou 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