{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T01:27:45Z","timestamp":1755221265082,"version":"3.43.0"},"reference-count":4,"publisher":"Wiley","issue":"2-3","license":[{"start":{"date-parts":[[2024,10,20]],"date-time":"2024-10-20T00:00:00Z","timestamp":1729382400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>An infant presents in extremis. After the medical team stabilizes him, the race is on to figure out why he got so sick in the first place. The consulting genetics team thinks that it is unlikely his problems are due to a genetic cause, but his extreme, confounding presentation is enough to justify trio exome sequencing. When the results reveal an unexpected, paternally inherited variant of uncertain significance (VUS) in <jats:italic>NOTCH3<\/jats:italic>, fresh questions arise. The infant's presenting symptoms and descriptive diagnoses, including hematemesis, epistaxis, and gastric ulcers, certainly do not fit the mold of CADASIL. However, closer inspection of his family history yields tantalizing clues: a father and paternal grandfather with seizures, and a\u00a0paternal grandfather with unexplained mood disturbances in middle age. Combining details gleaned from the family history and medical literature, the clinical genetics and laboratory genetics team collaborated, reclassified the VUS as likely pathogenic, and offered a new unifying diagnosis to explain much of the family's lore.<\/jats:p>","DOI":"10.1002\/ajmg.c.32117","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T02:19:29Z","timestamp":1729477169000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Family Lore, a Variant of Uncertain Significance, and\u00a0<scp>CADASIL<\/scp>"],"prefix":"10.1002","volume":"196","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9414-9540","authenticated-orcid":false,"given":"Rhys","family":"Duarte","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liesbeth","family":"Vossaert","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Baylor Genetics Laboratories  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra A.","family":"Darilek","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chelsi","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evan","family":"Schauer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Parobek","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Bland","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keren","family":"Machol","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Mizerik","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9781-3387","authenticated-orcid":false,"given":"Chaya N.","family":"Murali","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Texas USA"},{"name":"Department of Genetics Texas Children's Hospital  Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,20]]},"reference":[{"key":"e_1_2_4_2_1","unstructured":"Hack R. 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A.Lesnik Oberstein.2000.\u201cCADASIL Synonym: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy.\u201d"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.08.009"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13917"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u2010444\u201064076\u20105.00047\u20108"}],"container-title":["American Journal of Medical Genetics Part C: Seminars in Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.c.32117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T13:40:32Z","timestamp":1754660432000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.c.32117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,20]]},"references-count":4,"journal-issue":{"issue":"2-3","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/ajmg.c.32117"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.c.32117","archive":["Portico"],"relation":{},"ISSN":["1552-4868","1552-4876"],"issn-type":[{"type":"print","value":"1552-4868"},{"type":"electronic","value":"1552-4876"}],"subject":[],"published":{"date-parts":[[2024,10,20]]},"assertion":[{"value":"2024-08-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e32117"}}