{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T03:28:43Z","timestamp":1782790123486,"version":"3.54.5"},"reference-count":17,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Coffin\u2013Lowry syndrome (CLS) is a rare X\u2010linked disorder characterized by moderate to severe intellectual disability, hypotonia, craniofacial features, tapering digits, short stature, and skeletal deformities. Using whole exome sequencing and high\u2010resolution targeted comparative genomic hybridization array analysis, we identified a novel microduplication encompassing exons five through nine of <jats:italic>RPS6KA3<\/jats:italic> in three full brothers. Each brother presented with intellectual disability and clinical and radiographic features consistent with CLS. qRT\u2010PCR analyses performed on mRNA from the peripheral blood of the three siblings revealed a marked reduction of <jats:italic>RPS6KA3<\/jats:italic> levels suggesting a loss\u2010of\u2010function mechanism. PCR analysis of the patients\u2019 cDNA detected a band greater than expected for an exon 4\u201310 amplicon, suggesting this was likely a direct duplication that lies between exons 4 through 10, which was later confirmed by Sanger sequencing. This microduplication is only the third intragenic duplication of <jats:italic>RPS6KA3<\/jats:italic>, and the second and smallest reported to date thought to cause CLS. Our study further supports the clinical utility of methods such as next\u2010generation sequencing and high\u2010resolution genomic arrays to detect small intragenic duplications. These methods, coupled with expression studies and cDNA structural analysis have the capacity to confirm the diagnosis of CLS in these rare cases.<\/jats:p>","DOI":"10.1002\/ajmg.a.61353","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T07:10:08Z","timestamp":1568272208000},"page":"2357-2364","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An unusual cause for Coffin\u2013Lowry syndrome: Three brothers with a novel microduplication in <i>RPS6KA3<\/i>"],"prefix":"10.1002","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-5175","authenticated-orcid":false,"given":"Valerie J.","family":"Castelluccio","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Vetrini","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ty","family":"Lynnes","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Jones","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynda","family":"Holloway","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyce","family":"Belonis","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Cincinnati Children's Hospital Medical Center  Cincinnati Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M.","family":"Breman","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett H.","family":"Graham","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Sapp","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles E.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center  Greenwood South Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria M.","family":"Pratt","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-8995","authenticated-orcid":false,"given":"David D.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,9,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2015.106"},{"issue":"3","key":"e_1_2_6_3_1","first-page":"205","article-title":"Mental retardation with osteocartilaginous anomalies","volume":"112","author":"Coffin G. 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