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This report represents the largest cohort to\u2010date of rare\n                    <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>\n                    conditions in which one of the disease\u2010causing alleles was inherited and one occurred de novo. Clinical and research staff at Stanford University, clinical sites of the Undiagnosed Diseases Network (\n                    <jats:styled-content style=\"fixed-case\">UDN<\/jats:styled-content>\n                    ) and Genomics Research to Elucidate the Genetics of Rare diseases (\n                    <jats:styled-content style=\"fixed-case\">GREGoR<\/jats:styled-content>\n                    ) Consortium, and a large clinical genetic testing laboratory were contacted to identify cases of an\n                    <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>\n                    diagnosis resulting from an inherited and de novo disease\u2010causing variant in trans. Fifteen cases of\n                    <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content>\n                    conditions caused by one inherited and one de novo variant in a gene consistent with the clinical phenotype were identified; all had undergone trio exome or genome sequencing with genetic confirmation of reported relationships. Variants were confirmed to be in trans in eight of the 15 cases. The de novo variant was confirmed (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097) or presumed (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097) to have arisen on the paternal allele in 14\/15 (93%) of cases. Phenotypic and\/or molecular evidence of an AR condition should prompt parental segregation analysis to inform diagnosis, recurrence risks, and variant classification. Additional studies are needed to determine the incidence of this phenomenon given the implications for the interpretation of genetic testing and counseling for AR conditions.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70162","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T04:09:29Z","timestamp":1776658169000},"page":"2052-2060","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["De Novo Variants Associated With Autosomal Recessive Conditions: Case Series and Implications for Genetic Testing and Counseling"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9425-3073","authenticated-orcid":false,"given":"Annie D.","family":"Niehaus","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Stanford School of Medicine  Stanford California 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