{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:42:40Z","timestamp":1787319760983,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Molecular genetics enables more precise diagnoses of skeletal dysplasia and other skeletal disorders (SDs). We investigated the clinical utility of multigene panel testing for 5011 unrelated individuals with SD in the United States (December 2019\u2013April 2022). Median (range) age was 8 (0\u201390) years, 70.5% had short stature and\/or disproportionate growth, 27.4% had a positive molecular diagnosis (MDx), and 30 individuals received two MDx. Genes most commonly contributing to MDx were\n                    <jats:italic>FGFR3<\/jats:italic>\n                    (16.9%),\n                    <jats:italic>ALPL<\/jats:italic>\n                    (13.0%), and\n                    <jats:italic>COL1A1<\/jats:italic>\n                    (10.3%). Most of the 112 genes associated with \u22651 MDx were primarily involved in signal transduction (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200935), metabolism (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200923), or extracellular matrix organization (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917). There were implications associated with specific care\/treatment options for 84.4% (1158\/1372) of MDx\u2010positive individuals; &gt;50% were linked to conditions with targeted therapy approved or in clinical development, including osteogenesis imperfecta, achondroplasia, hypophosphatasia, and mucopolysaccharidosis. Forty individuals with initially inconclusive results became MDx\u2010positive following family testing. Follow\u2010up mucopolysaccharidosis enzyme activity testing was positive in 14 individuals (10 of these were not MDx\u2010positive). Our findings showed that inclusion of metabolic genes associated with SD increased the clinical utility of a gene panel and confirmed that integrated use of comprehensive gene panel testing with orthogonal testing reduced the burden of inconclusive results.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63646","type":"journal-article","created":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T02:29:49Z","timestamp":1714789789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Clinical utility of comprehensive gene panel testing for common and rare causes of skeletal dysplasia and other skeletal disorders: Results from the largest cohort to date"],"prefix":"10.1002","volume":"194","author":[{"given":"Gretchen","family":"MacCarrick","sequence":"first","affiliation":[{"name":"McKusick\u2010Nathans Department of Genetic Medicine Johns Hopkins University School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swaroop","family":"Aradhya","sequence":"additional","affiliation":[{"name":"Invitae Corporation  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitch","family":"Bailey","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorna","family":"Chu","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Hunt","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Izzo","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc  Novato California 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e","family":"Shediac","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc  Novato California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klane K.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedic Surgery Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Invitae Corporation  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Seratti","sequence":"additional","affiliation":[{"name":"BioMarin Pharmaceutical Inc  Novato California 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