{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:04:05Z","timestamp":1790708645329,"version":"4.1.0"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cenani\u2013Lenz syndactyly syndrome (CLSS, OMIM 212780) is a rare autosomal recessive disorder characterized by syndactyly and oligodactyly of the digits, fusion of carpal and tarsal bones, and radioulnar synostosis. Craniofacial anomalies and renal malformations have been reported in approximately half of cases, with variable expression. The condition results from homozygous or compound heterozygous mutations in the\n                    <jats:italic>LRP4<\/jats:italic>\n                    gene. We identified a consanguineous family with four individuals affected by CLSS, comprising two brothers and their two maternal male cousins. All patients presented with bilateral complex syndactyly, characterized by absent phalanges, reduced and disorganized metacarpals, and cutaneous toe syndactyly. The 2\u2010year\u2010old proband had a horseshoe kidney, whereas his 6\u2010year\u2010old cousin presented with right renal agenesis. None of the patients exhibited growth and developmental delay, cardiac anomalies, or intellectual disability. Based on the clinical suspicion of CLSS, targeted next\u2010generation sequencing of the\n                    <jats:italic>LRP4<\/jats:italic>\n                    gene was performed. This analysis revealed a biallelic variant, c.3830G&gt;T (NM_002334.3), resulting in the protein change p.Arg1277Leu, which has not been previously described. CLSS is a rare congenital disorder affecting distal limb development and is frequently associated with renal malformations and variable dysmorphic features. In this report, we describe four affected individuals carrying a novel homozygous missense variant in the\n                    <jats:italic>LRP4<\/jats:italic>\n                    gene, thereby broadening the clinical and genetic spectrum of CLSS and highlighting the pathogenic significance of this newly identified variant.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70208","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:30:59Z","timestamp":1779193859000},"page":"2273-2278","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Genetic Testing Uncovers a Novel\n                    <i>LRP4<\/i>\n                    Variant in Cenani\u2013Lenz Syndactyly Syndrome"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2381-3699","authenticated-orcid":false,"given":"Gamze Mutlucan","family":"K\u00f6seo\u011flu","sequence":"first","affiliation":[{"name":"Ankara Bilkent City Hospital, Pediatric Genetics Clinic  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-1809","authenticated-orcid":false,"given":"Esra","family":"K\u0131l\u0131\u00e7","sequence":"additional","affiliation":[{"name":"Ankara Bilkent City Hospital, Pediatric Genetics Clinic  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.05.004"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.60694"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399\u20100004.2001.590312.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00438491"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2023.148705"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010013\u20101331\u20102"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.2319"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCD.0b013e328306a6ed"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010021\u201000995\u2010x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2013.04.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.190330"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.03.004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36647"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ocl.2015.08.015"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_17_1","first-page":"41","article-title":"A Variant of Cenani\u2010Lenz Type Syndactyly","volume":"11","author":"Seven M.","year":"2000","journal-title":"Genetic Counseling (Geneva, Switzerland)"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605\u2010200304000\u201000001"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70208","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70208","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70208","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:14:57Z","timestamp":1790705697000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,19]]},"references-count":17,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/ajmg.a.70208"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70208","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,19]]},"assertion":[{"value":"2025-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}