{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T07:06:46Z","timestamp":1775804806718,"version":"3.50.1"},"reference-count":5,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"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":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Stickler syndrome (SS) is clinically and genetically heterogeneous. Autosomal recessive Stickler syndrome (ARSS) is characterized by sensorineural hearing loss, myopia, retinal degeneration, vitreous anomalies, and epiphyseal dysplasia. It may also include midfacial hypoplasia, cleft palate, and skeletal manifestations. Currently, only 40 ARSS cases have been described, and just 4 are linked to pathogenic variants in the\n LOXL3<\/jats:italic>\n gene. A 20\u2010year\u2010old woman was referred to Medical Genetics due to Pierre Robin sequence, myopia, hearing loss, and distinct features. She was evaluated in early childhood with her sisters but was discharged without a specific genetic diagnosis. Polyhydramnios was detected in prenatal ultrasounds. Delivery occurred at 35\u2009weeks. At birth, Pierre Robin sequence was evident, and she was admitted due to apnea. Complementary tests included karyotype, FISH 22q11, and screening for associated anomalies (cardiology, ophthalmology, ABR, and abdominal and cranial ultrasounds), all of which were normal. She had delayed speech development. She presents high myopia and bilateral conductive hearing loss, as well as nonspecific joint pain. She has two sisters with overlapping phenotypes. Both had cleft palate repair (one also with Pierre Robin sequence) and high\u2010degree myopia. The first had a ventricular septal defect that spontaneously closed at age 5, and the second has conductive hearing loss. The physical examination highlights: microcephaly (head circumference\u2009<\u2009p1, \u22122.5 SD), downward\u2010slanting palpebral fissures, midfacial and nasal ala hypoplasia, flat nasal bridge, elongated and flat philtrum, high\u2010arched palate, absent uvula, joint hypermobility, shortening of third\u2013fifth metacarpals and metatarsals, wide feet, and bilateral hallux valgus. Targeted sequencing of SS\u2010associated genes revealed a likely pathogenic variant c.1735C>T and a variant of uncertain significance c.956G>A in the\n LOXL3<\/jats:italic>\n gene. Affected sisters carry both variants; both parents are healthy carriers. We report three new cases of SS due to previously undescribed biallelic variants in the\n LOXL3<\/jats:italic>\n gene. The clinical features are similar to those observed in other SS patients; however, digital anomalies and microcephaly have not been previously reported in patients with LOXL3 variants, thus expanding the phenotypic spectrum. This case highlights the importance of re\u2010evaluating patients in light of ongoing advances in genetic diagnostics.\n <\/jats:p>","DOI":"10.1111\/cge.70087","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T01:10:21Z","timestamp":1759799421000},"page":"762-766","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Three New Cases of Autosomal Recessive Stickler Syndrome due to Biallelic Variants in the\n \n LOXL3<\/i>\n <\/scp>\n Gene"],"prefix":"10.1111","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5845-2853","authenticated-orcid":false,"given":"Carmen Mar\u00eda Dolores","family":"S\u00e1nchez","sequence":"first","affiliation":[{"name":"Hospital Cl\u00ednico Universitario Virgen de la Arrixaca El Palmar Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9574-1674","authenticated-orcid":false,"given":"Mar\u00eda Jos\u00e9 S\u00e1nchez","family":"Soler","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universitario Virgen de la Arrixaca El Palmar Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica El Palmar Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-3203","authenticated-orcid":false,"given":"Mar\u00eda","family":"del Carmen Mart\u00ednez Romero","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universitario Virgen de la Arrixaca El Palmar Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Doval","family":"Calvo","sequence":"additional","affiliation":[{"name":"Hospital General Universitario Santa Luc\u00eda Cartagena Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Juliana Ballesta","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednico Universitario Virgen de la Arrixaca El Palmar Spain"},{"name":"Instituto Murciano de Investigaci\u00f3n Biom\u00e9dica El Palmar Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1993","volume-title":"GeneReviews","author":"Mortier G.","year":"2000"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes13071135"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2020.8723"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/10556656211052781"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.04.003"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70087","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.70087","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.70087","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:16:27Z","timestamp":1775801787000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.70087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,6]]},"references-count":5,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/cge.70087"],"URL":"https:\/\/doi.org\/10.1111\/cge.70087","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.70087\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70087\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.70087\/v1\/review1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,6]]},"assertion":[{"value":"2025-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}