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Incomplete fill-in of the C-rich telomeric strand after DNA replication has been proposed as a mechanism for Coats plus syndrome, a phenotype within the broader spectrum of telomere biology disorders (TBD). Coats plus syndrome has so far been associated with pathogenic variants in <jats:italic>POT1<\/jats:italic>, <jats:italic>CTC1<\/jats:italic>, and <jats:italic>STN1<\/jats:italic>. Here we report the findings of biallelic deleterious rare variants in <jats:italic>POLA2<\/jats:italic> gene detected by whole genome sequencing and segregation analysis in five young adults from two unrelated families. All five individuals displayed abnormally short telomeres and a clinical phenotype suggesting a TBD disorder with Coats plus features including retinal and gastrointestinal telangiectasias. Our results suggest <jats:italic>POLA2<\/jats:italic> as a novel autosomal recessive gene for a TBD with Coats plus features.<\/jats:p>","DOI":"10.1038\/s41431-024-01722-8","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T04:15:47Z","timestamp":1732940147000},"page":"580-587","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of biallelic POLA2 variants in two families with an autosomal recessive telomere biology disorder"],"prefix":"10.1038","volume":"33","author":[{"given":"Malin","family":"Kvarnung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pettersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pattra","family":"Chun-on","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7118-3412","authenticated-orcid":false,"given":"Maryam","family":"Rafati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-1453","authenticated-orcid":false,"given":"Lisa J.","family":"McReynolds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Norberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0493-5394","authenticated-orcid":false,"given":"Pedro Luis","family":"Moura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Pesonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza","family":"Chaireti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boa","family":"Gr\u00f6nros S\u00f6derholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Burlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Ryd\u00e9n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Hellstr\u00f6m","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Giri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6006-0740","authenticated-orcid":false,"given":"Sharon A.","family":"Savage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suneet","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3285-4281","authenticated-orcid":false,"given":"Ann","family":"Nordgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-2507","authenticated-orcid":false,"given":"Bianca","family":"Tesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"1722_CR1","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/s41576-022-00527-z","volume":"24","author":"P Revy","year":"2023","unstructured":"Revy P, Kannengiesser C, Bertuch AA. Genetics of human telomere biology disorders. Nat Rev Genet. 2023;24:86\u2013108.","journal-title":"Nat Rev Genet"},{"key":"1722_CR2","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1182\/hematology.2022000394","volume":"2022","author":"SA Savage","year":"2022","unstructured":"Savage SA. Dyskeratosis congenita and telomere biology disorders. Hematology. 2022;2022:637\u201348.","journal-title":"Hematology"},{"key":"1722_CR3","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.ajhg.2012.02.002","volume":"90","author":"A Polvi","year":"2012","unstructured":"Polvi A, Linnankivi T, Kivel\u00e4 T, Herva R, Keating JP, M\u00e4kitie O, et al. Mutations in CTC1, encoding the CTS telomere maintenance complex Component 1, cause cerebroretinal microangiopathy with calcifications and cysts. 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Consent was obtained from all study participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}