{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T23:05:48Z","timestamp":1768518348619,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"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":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The dyskerin encoding gene <jats:italic>DKC1<\/jats:italic> plays an important role in telomerase activity and telomere maintenance. Pathogenic variants in <jats:italic>DKC1<\/jats:italic> cause an X\u2010linked multiorgan disease called dyskeratosis congenita (DC), the most severe form of which is Hoyeraal\u2013Hreidarsson syndrome (HHS). HHS due to <jats:italic>DKC1<\/jats:italic> variants has so far only been reported in hemizygous males and is associated with severe neurological impairment and progressive bone marrow failure, often causing lethality in early childhood. Heterozygous carrier females are often phenotypically normal. Here, we report a young adult female carrying a de novo splice\u2010site variant in <jats:italic>DKC1<\/jats:italic> and presenting with clinical features overlapping with HHS, such as intrauterine and postnatal growth retardation, microcephaly, intellectual disability, and recurrent infections, while lacking other typical aspects such as dermatological manifestations, cerebellar hypoplasia, or bone marrow failure. Aberrant splicing was confirmed with an in\u00a0vitro assay, and further analysis revealed very short telomere lengths in the individual, supporting a causative role of the <jats:italic>DKC1<\/jats:italic> variant. Our observations therefore suggest that heterozygous splice\u2010site variants in <jats:italic>DKC1<\/jats:italic> leading to loss of function might result in a phenotype overlapping with but not being typical for HHS in females, supporting a potential genotype\u2013phenotype correlation.<\/jats:p>","DOI":"10.1002\/ajmg.a.64097","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T07:39:17Z","timestamp":1745393957000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["De Novo Splice\u2010Site Variant in <scp><i>DKC1<\/i><\/scp> in a Female With Clinical Features of Hoyeraal\u2013Hreidarsson Syndrome"],"prefix":"10.1002","volume":"197","author":[{"given":"Dominique","family":"Braun","sequence":"first","affiliation":[{"name":"Department of Human Genetics Inselspital Bern, University of Bern  Bern 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Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"Kraus","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, Universit\u00e4tsklinikum Erlangen, Friedrich\u2010Alexander\u2010Universit\u00e4t Erlangen\u2010N\u00fcrnberg  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudine","family":"Rieubland","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Inselspital Bern, University of Bern  Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8002-2020","authenticated-orcid":false,"given":"Christiane","family":"Zweier","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Inselspital Bern, University of Bern  Bern Switzerland"},{"name":"Department for BioMedical Research (DBMR) University of Bern  Bern 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