{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T06:57:10Z","timestamp":1761980230385,"version":"build-2065373602"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T00:00:00Z","timestamp":1396828800000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Metacarpal 4\u20135 fusion (MF4; MIM#309630) is a rare congenital malformation of the hand characterized by the partial or complete fusion of the fourth and fifth metacarpals. The anomaly occurs as an isolated trait or part of a genetic syndrome. Recently, we have identified <jats:italic>FGF16<\/jats:italic> nonsense mutations as the underlying cause of isolated X\u2010linked recessive MF4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this report, we provide a detailed clinical description of a sporadic male patient showing MF4 in whom we performed Sanger sequencing of the entire coding sequence of <jats:italic>FGF16<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In addition to MF4 symptoms, the patient presented with generalized joint laxity and hypermobility. <jats:italic>FGF16<\/jats:italic> sequencing detected a novel truncating mutation (c.474_477del; p.E158DfsX25) in exon 3 of the gene. A heterozygous mutation was found in a clinically and radiologically unaffected mother of the proband.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our finding confirms that truncating mutations of <jats:italic>FGF16<\/jats:italic> are causative for X\u2010linked recessive metacarpal 4\u20135 fusion. Importantly, the mutation detected in this study was located in last exon of the gene (exon 3), like the only two <jats:italic>FGF16<\/jats:italic> disease\u2010causing variants identified to date. Thus, all <jats:italic>FGF16<\/jats:italic> mutations known to give rise to this rare skeletal hand malformation are C\u2010terminal and most probably do not result in a nonsense mediated decay. Additionally, our proband showed mild symptoms of a connective tissue disorder, as some other patients previously reported to have X\u2010linked MF4. Therefore, we suggest that impaired <jats:italic>FGF16<\/jats:italic> function may also be responsible for connective tissue symptoms in MF4 patients. Birth Defects Research (Part A) 100:314\u2013318, 2014. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.23239","type":"journal-article","created":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T10:19:13Z","timestamp":1396865953000},"page":"314-318","source":"Crossref","is-referenced-by-count":4,"title":["Further evidence for <i>FGF16<\/i> truncating mutations as the cause of X\u2010linked recessive fusion of metacarpals 4 \/ 5"],"prefix":"10.1002","volume":"100","author":[{"given":"Aleksander","family":"Jamsheer","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences Poznan Poland"},{"name":"NZOZ Center for Medical Genetics GENESIS Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"\u015amigiel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Rare Disorders Wroclaw Medical University Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Jakubiak","sequence":"additional","affiliation":[{"name":"Department of Genetics Wroclaw Medical University Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Zemojtel","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences Poznan Poland"},{"name":"Institute for Medical Genetics and Human Genetics, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Socha","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Poznan University of Medical Sciences Poznan Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter N.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Mundlos","sequence":"additional","affiliation":[{"name":"Institute for Medical Genetics and Human Genetics, Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Max Planck Institute for Molecular Genetics Berlin Germany"},{"name":"Berlin\u2010Brandenburg Center for Regenerative Therapies (BCRT) Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,7]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320520230"},{"key":"e_1_2_6_3_1","first-page":"521","article-title":"Familial synostosis of metacarpi IV and V","volume":"100","author":"Habighorst LV","year":"1965","journal-title":"Z Orthop Ihre Grenzgeb"},{"key":"e_1_2_6_4_1","first-page":"562","article-title":"Metacarpal 4\u20105 fusion with X\u2010linked recessive inheritance","volume":"24","author":"Holmes LB","year":"1972","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0072-968X(83)80015-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2004.08.007"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101659"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.12.002"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.20382"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.06.029"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06876"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.11.1571"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.7.4251"},{"key":"e_1_2_6_14_1","first-page":"244","article-title":"Kleine Beitrage zur Vererbungswissenschaft. 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