{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T07:39:15Z","timestamp":1781077155063,"version":"3.54.1"},"reference-count":14,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T00:00:00Z","timestamp":1623283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Coats plus syndrome (CP) is a rare autosomal recessive disorder, characterised by retinal telangiectasia exudates (Coats disease), leukodystrophy, distinctive intracranial calcification and cysts, as well as extra\u2010neurological features including abnormal vasculature of the gastrointestinal tract, portal hypertension and osteopenia with a tendency to fractures. CP most frequently occurs due to loss\u2010of\u2010function mutations in <jats:italic>CTC1<\/jats:italic>. The encoded protein CTC1 constitutes part of the CST (CTC1\u2010STN1\u2010TEN1) complex, and three patients have been described with CP due to biallelic mutations in <jats:italic>STN1<\/jats:italic>. Together with the identification of homozygosity for a specific loss\u2010of\u2010function mutation in <jats:italic>POT1<\/jats:italic> in a sibling pair, these observations highlight a defect in the maintenance of telomere integrity as the cause of CP, although the precise mechanism leading to the micro\u2010vasculopathy seen at a pathological level remains unclear. Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding. Genome sequencing revealed compound heterozygous variants in <jats:italic>STN1<\/jats:italic> as the likely genetic cause of CP in this present case.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We assessed the phenotype to be CP and undertook targeted sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whilst sequencing of <jats:italic>CTC1<\/jats:italic> and <jats:italic>POT1<\/jats:italic> was normal, we identified novel compound heterozygous variants in <jats:italic>STN1<\/jats:italic> (previous gene symbol <jats:italic>OBFC1<\/jats:italic>): one loss\u2010of\u2010function\u2013\u2013c.894dup (p.(Asp299Argfs*58)); and one missense\u2013\u2013c.707T&gt;C (p.(Leu236Pro)).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Given the clinical phenotype and identified variants we suggest that this is only the fourth patient reported to date with CP due to mutations in <jats:italic>STN1<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1708","type":"journal-article","created":{"date-parts":[[2021,6,10]],"date-time":"2021-06-10T22:39:59Z","timestamp":1623364799000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Novel compound heterozygous <i>STN1<\/i> variants are associated with Coats Plus syndrome"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0330-6585","authenticated-orcid":false,"given":"Tanvi","family":"Acharya","sequence":"first","affiliation":[{"name":"School of Clinical Medicine Cambridge University Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen V.","family":"Firth","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Addenbrooke\u2019s Hospital Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa","family":"Dugar","sequence":"additional","affiliation":[{"name":"Paediatric Liver, GI and Nutrition Centre and Mowat Labs King\u2019s College Hospital NHS Foundation Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tassos","family":"Grammatikopoulos","sequence":"additional","affiliation":[{"name":"Paediatric Liver, GI and Nutrition Centre and Mowat Labs King\u2019s College Hospital NHS Foundation Trust London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Seabra","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics and Neuroinflammation Institut Imagine Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angharad","family":"Walters","sequence":"additional","affiliation":[{"name":"Cambridgeshire Community Services Brooksfield Hospital Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanick J.","family":"Crow","sequence":"additional","affiliation":[{"name":"Centre for Genomic and Experimental Medicine MRC Institute of Genetics and Molecular Medicine University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alasdair P. J.","family":"Parker","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine Cambridge University Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.1084"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-43552"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.010"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)38288-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3661"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30578"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24193"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.5.1297"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61737"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20151618"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.215"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.276873.115"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1988.56"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1708","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mgg3.1708","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.1708","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:50:23Z","timestamp":1693198223000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.1708"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,10]]},"references-count":14,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1002\/mgg3.1708"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.1708","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,10]]},"assertion":[{"value":"2020-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1708"}}