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One\u2010hundred\u2010one patients had PC (<jats:italic>n<\/jats:italic>\u00a0=\u00a055), PS (<jats:italic>n<\/jats:italic>\u00a0=\u00a029), or AT deficiency (<jats:italic>n<\/jats:italic>\u00a0=\u00a018). One overlapping case had PC\u2010 and PS\u2010monoallelic variant. Fifty\u2010five PC\u2010deficient patients (54%) had 26 monoallelic or 29 biallelic variant(s), and 29 (29%) PS\u2010deficient patients had 20 monoallelic or nine biallelic variant(s). None of the patients had AT\u2010biallelic variants. The frequent low\u2010risk allele p.K193del (PC\u2010Tottori) was found in five patients with monoallelic (19%) but not 29 with biallelic variant(s). The most common low\u2010risk allele p.K196E (PS\u2010Tokushima) was found in five with monoallelic (25%) and six with biallelic variant(s) (67%). One exceptional de novo PC variant was found in 32 families with EOT. Only five parents had a history of thromboembolism. Thrombosis concurrently developed in three mother\u2013newborn pairs (two PC deficiency and one AT deficiency). The prospective cohort revealed the outcomes of 35 patients: three deaths with PC deficiency and 20 complication\u2010free survivors. Neurological complications were more frequently found in patients with PC\u2010biallelic variants than those with PC\u2010, PS\u2010, or AT\u2010monoallelic variants (73% vs. 24%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.019).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrate the need for elective screening for EOT targeting PC deficiency in Japan. Early prenatal diagnosis of PC deficiency in mother\u2013infant pairs may prevent perinatal thrombosis in them.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.30824","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T03:54:29Z","timestamp":1703822069000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The clinical and genetic landscape of early\u2010onset thrombophilia in Japan"],"prefix":"10.1002","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2602-7984","authenticated-orcid":false,"given":"Naoki","family":"Egami","sequence":"first","affiliation":[{"name":"Department of Pediatrics Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Ishimura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medical Sciences Kyushu 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