{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:08:00Z","timestamp":1790190480569,"version":"4.1.0"},"reference-count":8,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"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":["Clinical Genetics"],"published-print":{"date-parts":[[2023,4]]},"abstract":"Abstract<\/jats:title>To suggest a unique missense variant candidate based on long\u2010term ophthalmological changes and associated systemic signs described in five patients from two unrelated families affected by an autosomal dominant multi\u2010systemic disorder including Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anhidrosis and migraine Headaches, called ROSAH syndrome, related to a unique missense variant in ALPK1<\/jats:italic> gene. Observational longitudinal follow\u2010up study of unrelated families. Clinical analysis of ophthalmological and systemic examinations was performed, followed by genetic analysis, including targeted Next Generation Sequencing (NGS) and Whole\u2010Genome Sequencing (WGS). The ophthalmological phenotype showed extensive optic nerve swelling associated with early macular oedema and vascular leakage. The main associated systemic manifestations were recurrent fever, splenomegaly, anhidrosis, mild cytopenia, anicocytosis and hypersegmented polynuclear cells. WGS, shortened in the second family by the gene candidate suggestion, revealed in all patients the heterozygous missense variant c.710C>T; p.(Thr237Met) in ALPK1<\/jats:italic>. The primary morbidity in ROSAH syndrome in this cohort appeared ophthalmological. Comprehensive, detailed phenotype changes aided by the advancement in genetic testing could allow an early genetic diagnosis of ROSAH syndrome and targeted treatment. The unique missense variant may be suggested as a target of gene correction therapy.<\/jats:p>","DOI":"10.1111\/cge.14286","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T02:35:55Z","timestamp":1671676555000},"page":"453-458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["ROSAH<\/scp> syndrome mimicking chronic uveitis"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1935-2711","authenticated-orcid":false,"given":"Christine","family":"Fardeau","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Reference Center for Rare Diseases, La Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Paris\u2010Sorbonne University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munirah","family":"Alafaleq","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center for Rare Diseases, La Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Paris\u2010Sorbonne University Paris France"},{"name":"Ophthalmology Department Imam Abdulrahman Bin Faisal University, King Fahad Hospital of the University Dammam Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire\u2010Marie","family":"Dhaenens","sequence":"additional","affiliation":[{"name":"University Lille, Inserm, CHU Lille, U1172\u2010LilNCog\u2010Lille Neuroscience & Cognition Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Dollfus","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique m\u00e9dicale d'Alsace, CARGO Reference Center for Rare Diseases in Genetic Ophthalmology University Hospital of Strasbourg Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Kon\u00e9\u2010Paut","sequence":"additional","affiliation":[{"name":"Paediatric Rheumatology Department and CEREMAIA, Bicetre Hospital, APHP University of Paris Sud Saclay Bures\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Grunewald","sequence":"additional","affiliation":[{"name":"University Lille, Inserm, CHU Lille, U1172\u2010LilNCog\u2010Lille Neuroscience & Cognition Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Baptiste","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Reference Center for Rare Diseases, La Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital Paris\u2010Sorbonne University Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherif","family":"Titah","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology H\u00f4pital Fondation Rothschild Paris 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0476-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34437"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2022-222629"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0433-3"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01214-8"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-021-01087-3"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00741-6"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.10.006"}],"container-title":["Clinical 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