{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:37:19Z","timestamp":1774672639296,"version":"3.50.1"},"reference-count":11,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Raine syndrome (MIM 259775) is a rare autosomal recessive disorder, first described by Raine et\u00a0al. in 1989, with an estimated prevalence of &lt;1\/1,000,000. This is due to pathogenic variants in <jats:italic>FAM2<\/jats:italic><jats:italic>0C<\/jats:italic> characterized by osteosclerosis, typical craniofacial features, and brain calcifications. Here, we report a novel variant in <jats:italic>FAM2<\/jats:italic><jats:italic>0C<\/jats:italic>, describe a uniquely severe craniofacial and CNS phenotype of Raine syndrome, and correlate it with prenatal findings. Fetal phenotyping was based on ultrasound and MRI. Solo exome sequencing was performed from DNA extracted from postmortem skin biopsy. Targeted parental variant testing was subsequently performed. A homozygous missense variant NM_020223.4 (c.1445\u00a0G\u00a0&gt;\u00a0A (p.Gly482Glu)) was identified in <jats:italic>FAM2<\/jats:italic><jats:italic>0C<\/jats:italic> associated with Raine syndrome. The infant had the characteristic dysmorphic features seen in Raine syndrome. He had particularly significant CNS manifestations consisting of multisuture craniosynostosis with protrusion of the brain parenchyma through fontanelles and cranial lacunae. Histological sections of the brain showed marked periventricular gliosis with regions of infarction, hemorrhage, and cavitation with global periventricular leukomalacia. Numerous dystrophic calcifications were diffusely present. Here, we demonstrate the identification of a novel variant in <jats:italic>FAM2<\/jats:italic><jats:italic>0C<\/jats:italic> in an infant with the characteristic features seen in Raine syndrome. The patient expands the characteristic phenotype of Raine syndrome to include a uniquely severe CNS phenotype, first identified on prenatal imaging.<\/jats:p>","DOI":"10.1002\/pd.6506","type":"journal-article","created":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T12:54:40Z","timestamp":1704113680000},"page":"369-372","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Raine syndrome: Prenatally identified severe craniofacial phenotype with multisuture synostosis and brain abnormalities associated with variants in <i>FAM2<\/i><i>0C<\/i>"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5937-9148","authenticated-orcid":false,"given":"Courtney P.","family":"Verscaj","sequence":"first","affiliation":[{"name":"Division of Newborn Medicine Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8439-9386","authenticated-orcid":false,"given":"Carly","family":"Smith","sequence":"additional","affiliation":[{"name":"Perinatal Diagnostic Center Stanford Children's Health  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Homeyer","sequence":"additional","affiliation":[{"name":"Perinatal Diagnostic Center Stanford Children's Health  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dena R.","family":"Matalon","sequence":"additional","affiliation":[{"name":"Perinatal Diagnostic Center Stanford Children's Health  Stanford California USA"},{"name":"Department of Pediatrics Division of Medical Genetics Stanford University  Stanford California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,1]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.07.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32022"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6637180"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61291"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010001\u20100469\u20105"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.5818"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11020222"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.3034"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.mcd.0000080413.95344.60"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002470050473"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320430522"}],"container-title":["Prenatal Diagnosis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pd.6506","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T02:05:56Z","timestamp":1710468356000},"score":1,"resource":{"primary":{"URL":"https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.6506"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":11,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/pd.6506"],"URL":"https:\/\/doi.org\/10.1002\/pd.6506","archive":["Portico"],"relation":{},"ISSN":["0197-3851","1097-0223"],"issn-type":[{"value":"0197-3851","type":"print"},{"value":"1097-0223","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"2023-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}