{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:47Z","timestamp":1753869407180,"version":"3.41.2"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T00:00:00Z","timestamp":1578009600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Syndactyly is a clinical feature of split\u2010hand foot malformation (SHFM), ectodermal\u2010dysplasia\u2010syndactyly (EDSS1) and Cenani\u2013Lenz syndactyly syndromes (CLSS). In EDSS1, only cutaneous syndactyly is observed, with sparse hair, abnormal nails and dentition. In SHFM, bony syndactyly may vary from hypoplasia of one phalanx to aplasia of central digits, extending to complete fusion of all fingers and toes in CLSS. Several genes have been assigned to these syndromes. Performing a single step molecular diagnostics becomes a challenge when a phenotype has overlaps with several syndromes or when some of the clinical features are not fully expressed in patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Whole exome sequencing (WES) analysis on one sample derived from a consanguineous family was performed. A causative variant in WES data was prioritized via standard bioinformatics tools. The selected variant was Sanger sequenced in all the available family members for autosomal recessive segregation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel missense variant (c.1151A&gt;G; p.Tyr384Cys) was identified in the <jats:italic>LRP4<\/jats:italic> gene. Sanger validation confirmed that all affected individuals were homozygous and the obligate carriers were heterozygous for this variant. The variant is neither reported in 1000 human genomes, nor in 60 706 exomes databases, and is predicted as \u201cpathogenic\u201d by SIFT, Polyphen\u20102 and MutationTaster software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study broadens the pathogenic spectrum of the <jats:italic>LRP4<\/jats:italic> gene in syndactyly syndromes. WES is a powerful tool for genetic analysis in research and can be readily used as a first\u2010line diagnostic test in syndactyly and related phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3143","type":"journal-article","created":{"date-parts":[[2019,11,21]],"date-time":"2019-11-21T16:33:41Z","timestamp":1574354021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Novel missense alteration in <i>LRP4<\/i> gene underlies Cenani\u2013Lenz syndactyly syndrome in a consanguineous family"],"prefix":"10.1002","volume":"22","author":[{"given":"Nuha","family":"Alrayes","sequence":"first","affiliation":[{"name":"Faculty of Applied Medical Science King Abdulaziz University  Jeddah 21589 Saudi Arabia"},{"name":"Princess Al\u2010Jawhara Center of Excellence in Research of Hereditary Disorders King Abdulaziz University  Jeddah Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdul","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Bioinformatics Khushal Khan Khattak University Karak  Khyber\u2010Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farman","family":"Ullah","sequence":"additional","affiliation":[{"name":"Department of Computer Science and Bioinformatics Khushal Khan Khattak University Karak  Khyber\u2010Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad","family":"Ishfaq","sequence":"additional","affiliation":[{"name":"Centre for Omic Sciences Islamia College Peshawar  Khyber\u2010Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Musharraf","family":"Jelani","sequence":"additional","affiliation":[{"name":"Princess Al\u2010Jawhara Center of Excellence in Research of Hereditary Disorders King Abdulaziz University  Jeddah Saudi Arabia"},{"name":"Centre for Omic Sciences Islamia College Peshawar  Khyber\u2010Pakhtunkhwa Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8818-5369","authenticated-orcid":false,"given":"Abdul","family":"Wali","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Life Sciences &amp; 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