{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:26:13Z","timestamp":1777389973396,"version":"3.51.4"},"reference-count":11,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"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 A"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>POLE<\/jats:italic> is a pleiotropic gene with phenotypic expression of pathogenic variants depending on the type of variant, impact on the protein, and mode of inheritance. Heterozygous missense variants located within the exonuclease domain have been shown to result in polymerase proofreading\u2010associated polyposis (PPAP) which is characterized by an increased risk for colon polyps and colorectal cancer. Biallelic variants resulting in markedly reduced amounts of normal protein have been reported in two separate recessive pediatric syndromes: facial dysmorphism, immunodeficiency, livedo, and short stature as well as intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenital, and genital anomalies. Here we report two siblings identified to have <jats:italic>POLE<\/jats:italic> c.1686\u2009+\u200932C\u2009&gt;\u2009G in trans with <jats:italic>POLE<\/jats:italic> p.(Glu709*) via exome sequencing. A detailed review of the reported phenotypes in these two siblings and from available literature revealed that individuals with biallelic <jats:italic>POLE<\/jats:italic> pathogenic variants resulting in partial loss\u2010of\u2010function present with a similar phenotype: short stature and facial dysmorphism with or without immunodeficiency. These data suggest a phenotypic continuum between the previously reported <jats:italic>POLE<\/jats:italic>\u2010related recessive disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.62908","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T07:36:49Z","timestamp":1658389009000},"page":"3121-3125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phenotypic continuum between <scp><i>POLE<\/i><\/scp>\u2010related recessive disorders: A case report and literature review"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0292-2557","authenticated-orcid":false,"given":"Maegan E.","family":"Roberts","sequence":"first","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"},{"name":"Division of Human Genetics, Department of Internal Medicine The Ohio State University  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Nimrichter","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan L.","family":"Marshall","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth K.","family":"Flynn","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick","family":"Person","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen S.","family":"Hruska","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-0875","authenticated-orcid":false,"given":"Paul","family":"Kruszka","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Juusola","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.41"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","unstructured":"Church J. M. (2014).Polymerase proofreading\u2010associated polyposis: a new dominantly inherited syndrome of hereditary colorectal cancer predisposition.Dis Colon Rectum 57(3) 396\u2013397.https:\/\/doi.org\/10.1097\/dcr.0000000000000084","DOI":"10.1097\/DCR.0000000000000084"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1276"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.10.024"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/em.21731"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0922-2"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121303"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2503"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10689-021-00256-y"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29396"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0177-y"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62908","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62908","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62908","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:43:55Z","timestamp":1708497835000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,21]]},"references-count":11,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/ajmg.a.62908"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62908","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,21]]},"assertion":[{"value":"2021-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}