{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T03:11:19Z","timestamp":1773717079184,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T00:00:00Z","timestamp":1594684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007928","name":"Ningbo Municipal Bureau of Science and Technology","doi-asserted-by":"publisher","award":["2018A610262"],"award-info":[{"award-number":["2018A610262"]}],"id":[{"id":"10.13039\/501100007928","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Polydactyly and syndactyly are digital abnormalities in limb\u2010associated birth defects usually caused by genetic disorders. In this study, a five\u2010generation Chinese pedigree was found with triphalangeal thumb polysyndactyly syndrome (TPTPS), showing an autosomal dominant pattern of inheritance. We utilized linkage analysis and whole genome sequencing (WGS) for the genetic diagnosis of this pedigree. Linkage analysis was performed using a genome\u2010wide single nucleotide polymorphism (SNP) chip and three genomic regions were identified in chromosomes 2, 6, and 7 with significant linkage signals. WGS discovered a copy number variation (CNV) mutation caused by a large duplication region at the tail of chromosome 7 located in exons 1\u20135 of the <jats:italic>LMBR1<\/jats:italic> gene, including the zone of polarizing activity regulatory sequence (ZRS), with a length of approximately 180\u2009kb. A real\u2010time polymerase chain reaction (PCR) assay confirmed the duplication. The findings of our study supported the notion that large duplications including the ZRS caused TPTPS. Our study showed that linkage analysis in combination with WGS could successfully identify the disease locus and causative mutation in TPTPS, which could help elucidate the molecular mechanisms and genotype\u2013phenotype correlations in polydactyly.<\/jats:p>","DOI":"10.1002\/ajmg.a.61757","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T08:57:55Z","timestamp":1594717075000},"page":"2117-2123","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Large duplication in <scp><i>LMBR1<\/i><\/scp> gene in a large Chinese pedigree with triphalangeal thumb polysyndactyly syndrome"],"prefix":"10.1002","volume":"182","author":[{"given":"Jihai","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Hand Surgery Ningbo No. 6 Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Huashan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofeng","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery Ningbo No. 6 Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Libing","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery Ningbo No. 6 Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huizong","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery Ningbo No. 6 Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaokun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Trauma Peking University People Hospital  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Ruijin Hospital North, School of Medicine Shanghai Jiaotong University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery Ningbo No. 6 Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Computational Biology SKLG, School of Life Sciences, Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7578-8483","authenticated-orcid":false,"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hand Surgery Ningbo No. 6 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