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Previous studies have revealed locus heterogeneity with rare variants in <jats:italic>DVL1<\/jats:italic>, <jats:italic>DVL3<\/jats:italic>, <jats:italic>FZD2<\/jats:italic>, <jats:italic>NXN<\/jats:italic>, <jats:italic>ROR2<\/jats:italic>, and <jats:italic>WNT5A<\/jats:italic> underlying the etiology of RS. The aforementioned \u201cRobinow\u2010associated genes\u201d and their gene products all play a role in the WNT\/planar cell polarity signaling pathway. We performed gene\u2010targeted Sanger sequencing, exome sequencing, genome sequencing, and array comparative genomic hybridization on four subjects with a clinical diagnosis of RS who had not had prior DNA testing. Individuals in our cohort were found to carry pathogenic or likely pathogenic variants in three RS related genes: <jats:italic>DVL1<\/jats:italic>, <jats:italic>ROR2<\/jats:italic>, and <jats:italic>NXN<\/jats:italic>. One subject was found to have a nonsense variant (c.817C\u2009&gt;\u2009T [p.Gln273*]) in <jats:italic>NXN in trans<\/jats:italic> with an ~1\u00a0Mb telomeric deletion on chromosome 17p containing <jats:italic>NXN<\/jats:italic>, which supports our contention that biallelic <jats:italic>NXN<\/jats:italic> variant alleles are responsible for a novel autosomal recessive RS locus. These findings provide increased understanding of the role of WNT signaling in skeletal development and maintenance. These data further support the hypothesis that dysregulation of the noncanonical WNT pathway in humans gives rise to RS.<\/jats:p>","DOI":"10.1002\/ajmg.a.61908","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T19:02:43Z","timestamp":1602615763000},"page":"3593-3600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Novel pathogenic genomic variants leading to autosomal dominant and recessive Robinow syndrome"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-5999","authenticated-orcid":false,"given":"Chaofan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6161-0510","authenticated-orcid":false,"given":"Juliana F.","family":"Mazzeu","sequence":"additional","affiliation":[{"name":"University of Brasilia  Brasilia Brazil"},{"name":"Robinow Syndrome Foundation  Anoka Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Eisfeldt","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"},{"name":"Center for Molecular Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Science for Life Laboratory Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-7720","authenticated-orcid":false,"given":"Christopher M.","family":"Grochowski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janson","family":"White","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"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 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalini N.","family":"Jhangiani","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna M.","family":"Muzny","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1356-5698","authenticated-orcid":false,"given":"Richard A.","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Lindstrand","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Molecular Medicine and Surgery Karolinska Institutet  Stockholm Sweden"},{"name":"Center for Molecular Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-9246","authenticated-orcid":false,"given":"James R.","family":"Lupski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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