{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:02:51Z","timestamp":1792612971339,"version":"4.5.0"},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,8,4]],"date-time":"2015-08-04T00:00:00Z","timestamp":1438646400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["U54HG006542"],"award-info":[{"award-number":["U54HG006542"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Klippel\u2013Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel\u2013Feil. Mutated genes for both dominant (<jats:italic>GDF6<\/jats:italic> and <jats:italic>GDF3<\/jats:italic>) and recessive (<jats:italic>MEOX1<\/jats:italic>) forms of Klippel\u2013Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left\u2013right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel\u2013Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in <jats:italic>RIPPLY2<\/jats:italic>, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating <jats:italic>Tbx6<\/jats:italic>. Our data confirm <jats:italic>RIPPLY2<\/jats:italic> as a novel gene for autosomal recessive Klippel\u2013Feil syndrome, and in addition\u2014from a mechanistic standpoint\u2014suggest the possibility that mutations in <jats:italic>RIPPLY2<\/jats:italic> could also lead to heterotaxy. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37263","type":"journal-article","created":{"date-parts":[[2015,8,4]],"date-time":"2015-08-04T05:29:15Z","timestamp":1438666155000},"page":"2795-2799","source":"Crossref","is-referenced-by-count":51,"title":["Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel\u2013Feil syndrome"],"prefix":"10.1002","volume":"167","author":[{"given":"Ender","family":"Karaca","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozge O.","family":"Yuregir","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Numune Training and Research Hospital Adana Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevcan T.","family":"Bozdogan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Mersin University Mersin Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huseyin","family":"Aslan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Medical Faculty of Eskisehir Osmangazi University Eskisehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davut","family":"Pehlivan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Human Genome Sequencing Center Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep C.","family":"Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Gambin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yavuz","family":"Bayram","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmed M.","family":"Atik","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serkan","family":"Erdin","sequence":"additional","affiliation":[{"name":"Center for Human Genetic Research Massachusetts General Hospital Boston Massachusetts"},{"name":"Program in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Muzny","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Human Genome Sequencing Center Baylor College of Medicine Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas"},{"name":"Human Genome Sequencing Center Baylor College of Medicine Houston 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