{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T21:35:03Z","timestamp":1768772103223,"version":"3.49.0"},"reference-count":20,"publisher":"BMJ","issue":"1","funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["GGP20070"],"award-info":[{"award-number":["GGP20070"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2019-12369368"],"award-info":[{"award-number":["RF-2019-12369368"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,11,11]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>Joubert syndrome (JS) is an inherited neurodevelopmental ciliopathy with wide clinical and genetic heterogeneity, whose paradigmatic sign is a peculiar cerebellar and brainstem malformation known as the \u2018molar tooth sign\u2019. Recessive pathogenic variants in the <jats:italic>HYLS1<\/jats:italic> gene are associated with hydrolethalus syndrome (HLS), a severe disorder characterised by multiple developmental defects leading to intrauterine or perinatal death. However, <jats:italic>HYLS1<\/jats:italic> biallelic variants were also reported in three individuals with JS.<\/jats:p>\n               <jats:p>Here, we report a fourth patient with a purely neurological JS carrying two compound heterozygous missense variants in the <jats:italic>HYLS1<\/jats:italic> gene. Notably, while all patients with lethal HLS had both variants falling within the highly conserved HYLS-1 Box, the four patients with milder JS phenotype featured at least one variant external to this evolutionary conserved domain, suggesting a possible correlation between the mutation site and the severity of the phenotype.<\/jats:p>","DOI":"10.1136\/jmg-2024-110308","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T13:15:53Z","timestamp":1733231753000},"page":"3-5","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Novel <i>HYLS1<\/i> variants associated with Joubert syndrome suggest potential genotype-phenotype correlates"],"prefix":"10.1136","volume":"62","author":[{"given":"Simone","family":"Gana","sequence":"first","affiliation":[{"name":"Neurogenetics Research Center, Fondazione Istituto Neurologico Nazionale C Mondino Istituto di Ricovero e Cura a Carattere Scientifico, 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