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Whole\u2010exome sequencing (WES), followed by segregation analysis using Sanger sequencing, revealed a heterozygous missense variant [c.G1696A, p.(Gly566Ser)] in the <jats:italic>LRP4<\/jats:italic> gene located on human chromosome 11p11.2. Homology protein modeling revealed the mutant Ser566 generated new interactions with at least four other amino acids and disrupted protein folding and function. Our findings demonstrated the first direct evidence of involvement of <jats:italic>LRP4<\/jats:italic> in causing polydactyly and phalangeal synostosis in the same family. This study highlighted the importance of inclusion of <jats:italic>LRP4<\/jats:italic> gene in screening individuals presenting polydactyly in hands and feet, and phalangeal synostosis in the same family.<\/jats:p>","DOI":"10.1111\/cga.12536","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T06:09:10Z","timestamp":1691734150000},"page":"190-194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A variant in the <scp>LDL<\/scp> receptor\u2010related protein encoding gene <scp><i>LRP4<\/i><\/scp> underlying polydactyly and phalangeal synostosis in a family of Pakistani origin"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1961-8105","authenticated-orcid":false,"given":"Hammal","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Biosciences COMSATS University Islamabad  Islamabad 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