{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:15:51Z","timestamp":1788315351244,"version":"build-2803163510"},"reference-count":5,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>CLDN11<\/jats:italic>\n                    has recently been associated with hypomyelinating leukodystrophy caused by de novo stop\u2010loss variants. Here, we present a new case involving a homozygous variant in order to expand the genetic and clinical spectrum of the disease. We performed a comprehensive clinical, neuroradiological, and genetic evaluation in a child presenting with global developmental delay. Brain MRI and MR spectroscopy were obtained, and next\u2010generation sequencing with parental segregation analysis was conducted. The patient presented with developmental delay, hypotonia, limb hypertonia, esotropia, and an absence of early developmental milestones in infancy, followed by partial motor improvement and persistent language and cognitive impairment. Brain MRI revealed diffuse supratentorial hypomyelination with stability over time. Genetic analysis identified a novel homozygous\n                    <jats:italic>CLDN11<\/jats:italic>\n                    start\u2010loss variant (c.1A&gt;G; p.Met1Val), which is predicted to result in biallelic loss of function. Both parents were found to be heterozygous carriers. This case supports an autosomal recessive mechanism of\n                    <jats:italic>CLDN11<\/jats:italic>\n                    \u2010related disease, which differs from the dominant stop\u2010loss variants reported previously. The phenotype partially overlaps with that of earlier cases, but is characterized by milder motor involvement and more pronounced cognitive impairment. These findings broaden the mutational spectrum and suggest distinct pathogenic mechanisms, with important implications for diagnosis and genetic counselling.\n                  <\/jats:p>","DOI":"10.1111\/cge.70212","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T02:55:26Z","timestamp":1784084126000},"page":"508-512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Claudin\u201011\u2013Mediated Hypomyelinating Leukodystrophy 22: New Insights Into Pathogenic Mechanisms"],"prefix":"10.1111","volume":"110","author":[{"given":"Fabio","family":"Acquaviva","sequence":"first","affiliation":[{"name":"Medical Genetics Unit, Department of General and Emergency Pediatrics AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Troisi","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Neurosciences Santobono\u2010Pausilipon Children's Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Errichiello","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Neurosciences Santobono\u2010Pausilipon Children's Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmela","family":"Russo","sequence":"additional","affiliation":[{"name":"Pediatric Neuroradiology Unit, Department of Neurosciences Santobono\u2010Pausilipon Children's Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio Maria","family":"Covelli","sequence":"additional","affiliation":[{"name":"Pediatric Neuroradiology Unit, Department of Neurosciences Santobono\u2010Pausilipon Children's Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Anna","family":"Siano","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of General and Emergency Pediatrics AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rosaria","family":"Manna","sequence":"additional","affiliation":[{"name":"Rehabilitation Unit, Department of Neurosciences Santobono\u2010Pausilipon Children's Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-1807","authenticated-orcid":false,"given":"Alfonsina","family":"Tirozzi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of General and Emergency Pediatrics AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"De Brasi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of General and Emergency Pediatrics AORN Santobono\u2010Pausilipon  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Varone","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, Department of Neurosciences Santobono\u2010Pausilipon Children's Hospital  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa410"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2023.1344090"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadva.2025.100159"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms27041956"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2024.06.010"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70212","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70212","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70212","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:53:55Z","timestamp":1788314035000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70212"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":5,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/cge.70212"],"URL":"https:\/\/doi.org\/10.1111\/cge.70212","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"assertion":[{"value":"2026-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}