{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:05:04Z","timestamp":1790388304103,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T00:00:00Z","timestamp":1687478400000},"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":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Skeletal dysplasias broadly include disorders of cartilage or bone. Omodysplasia\u20101 is a type of skeletal dysplasia caused by biallelic loss of function variants in the <jats:italic>GPC6<\/jats:italic> gene. <jats:italic>GPC6<\/jats:italic> codes for the protein glypican 6 (<jats:italic>GPC6<\/jats:italic>) (OMIM *604404), which stimulates bone growth. We report a family in which five out of nine children were presented with a skeletal dysplasia characterized phenotypically by mild short stature and rhizomelia. All affected individuals were found to have homozygous missense variants in <jats:italic>GPC6<\/jats:italic>: c.511 C&gt;T (p.Arg171Trp). Radiograph findings included rhizomelic foreshortening of all four extremities, coxa breva, and ulna minus deformity. Using a Hedgehog (Hh) reporter assay, we demonstrate that the variant found in this family results in significantly reduced stimulation of Hh activity when compared to the wild\u2010type <jats:italic>GPC6<\/jats:italic> protein, however protein function is still present. Thus, the milder phenotype seen in the family presented is hypothesized due to decreased <jats:italic>GPC6<\/jats:italic> protein activity versus complete loss of function as seen in omodysplasia\u20101. Given the unique phenotype and molecular mechanism, we propose that this family's findings widen the phenotypic spectrum of <jats:italic>GPC6<\/jats:italic>\u2010related skeletal dysplasias.<\/jats:p>","DOI":"10.1002\/ajmg.a.63337","type":"journal-article","created":{"date-parts":[[2023,6,25]],"date-time":"2023-06-25T01:30:02Z","timestamp":1687656602000},"page":"2571-2577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Five siblings expand the spectrum of <i>GPC6<\/i>\u2010related skeletal dysplasia"],"prefix":"10.1002","volume":"191","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0915-6154","authenticated-orcid":false,"given":"Molly M.","family":"Crenshaw","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Genetics and Metabolism University of Colorado School of Medicine (CU\u2010SOM)  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana L.","family":"Meyers","sequence":"additional","affiliation":[{"name":"Department of Radiology CU\u2010SOM  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics and Metabolism University of Colorado School of Medicine (CU\u2010SOM)  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Slegesky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics and Metabolism University of Colorado School of Medicine (CU\u2010SOM)  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6605-1028","authenticated-orcid":false,"given":"Jessica","family":"Duis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics and Metabolism University of Colorado School of Medicine (CU\u2010SOM)  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen R.","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics and Metabolism University of Colorado School of Medicine (CU\u2010SOM)  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margarita","family":"Saenz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics and Metabolism University of Colorado School of Medicine (CU\u2010SOM)  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Filmus","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics Sunnybrook Research Institute, University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi J. L.","family":"Meeks","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Genetics and Metabolism University of Colorado School of Medicine (CU\u2010SOM)  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000506384"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320580416"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.05.002"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201605119"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-003-1064-9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genom-090314-045904"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3181daae9b"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201008087"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.4.328"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-21-0557"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10555"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.38.26968"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63337","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,20]],"date-time":"2023-09-20T06:24:58Z","timestamp":1695191098000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,23]]},"references-count":12,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2023,10]]}},"alternative-id":["10.1002\/ajmg.a.63337"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63337","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,23]]},"assertion":[{"value":"2023-04-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-06-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}