{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:07Z","timestamp":1790524867658,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T00:00:00Z","timestamp":1453420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Osteogenesis imperfecta (OI) and Ehlers\u2013Danlos syndrome (EDS) are variable genetic disorders that overlap in different ways [Cole 1993; Grahame 1999]. Here, we describe a boy presenting with severe muscular hypotonia, multiple fractures, and joint hyperflexibility, features that are compatible with mild OI and hypermobility type EDS, respectively. By whole exome sequencing, we identified both a <jats:italic>COL1A1<\/jats:italic> mutation (c.4006\u20101G\u2009&gt;\u2009A) inherited from the patient's mildly affected mother and biallelic missense variants in <jats:italic>TNXB<\/jats:italic> (p.Val1213Ile, p.Gly2592Ser). Analysis of cDNA showed that the <jats:italic>COL1A1<\/jats:italic> splice site mutation led to intron retention causing a frameshift (p.Phe1336Valfs*72). Type 1 collagen secretion by the patient's skin fibroblasts was reduced. Immunostaining of a muscle biopsy obtained from the patient revealed a clear reduction of tenascin\u2010X in the extracellular matrix compared to a healthy control. These findings imply that the combination of the <jats:italic>COL1A1<\/jats:italic> mutation with the <jats:italic>TNXB<\/jats:italic> variants might cause the patient's unique phenotype. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37547","type":"journal-article","created":{"date-parts":[[2016,1,22]],"date-time":"2016-01-22T14:33:19Z","timestamp":1453473199000},"page":"1080-1085","source":"Crossref","is-referenced-by-count":16,"title":["An overlapping phenotype of Osteogenesis imperfecta and Ehlers\u2013Danlos syndrome due to a heterozygous mutation in <i>COL1A1<\/i> and biallelic missense variants in <i>TNXB<\/i> identified by whole exome sequencing"],"prefix":"10.1002","volume":"170","author":[{"given":"Luisa","family":"Mackenroth","sequence":"first","affiliation":[{"name":"Institute of Medical and Human Genetics Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"},{"name":"Faculty of Medicine Carl Gustav Carus Institute for 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