{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:32:35Z","timestamp":1792787555706,"version":"4.5.0"},"reference-count":45,"publisher":"Wiley","license":[{"start":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T00:00:00Z","timestamp":1689033600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Graduate Entrance Scholarship"},{"name":"Alberta Graduate Excellence Scholarship"},{"DOI":"10.13039\/501100009192","name":"Alberta Innovates","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009192","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012280","name":"Rare Disease Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000190","name":"University of Alberta","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shriners Chair in Scoliosis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2023,7,11]]},"abstract":"<jats:p>Scoliosis affects over four million Americans, with most cases having an idiopathic cause. Pathogenic variants in the LUNATIC FRINGE (LFNG) gene can cause spondylocostal dysostosis type-III (SCD3), which is a rare skeletal dysplasia characterized by the absence, fusion, or partial development of vertebrae and ribs. Acute restrictive lung disease and scoliosis may also be present in some cases. The variability in symptoms suggests that there may be other underlying pathological mechanisms that are yet to be discovered. We conducted an analysis of two novel LFNG variants, c.766G&gt;A (p.G256S) and c.521G&gt;A (p.R174H), that were observed in a patient with SCD3 phenotype and scoliosis. Characterizing these variants can help us better understand the relationship between genotype and phenotype. We assessed both variants for impaired glycosyltransferase activity, subcellular mislocalization, and aberrant pre-proprotein processing. Our results indicate that the p.G256S variant is enzymatically nonfunctional, while the p.R174H variant is functionally less effective. Both variants were correctly localized and processed. Our findings suggest that the hypomorphic variant (p.R174H) may have partially improved the patient\u2019s stature, as evidenced by a lower arm span-to-height ratio, increased height, and more vertebrae. However, this variant did not appear to have any effect on the severity of vertebral malformations, including scoliosis. Further research is necessary to determine the extent to which variations in LFNG activity affect the presentation of SCD3.<\/jats:p>","DOI":"10.1155\/2023\/5989733","type":"journal-article","created":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T18:35:07Z","timestamp":1689100507000},"page":"1-12","source":"Crossref","is-referenced-by-count":2,"title":["Functional Characterization of Novel Lunatic Fringe Variants in Spondylocostal Dysostosis Type-III with Scoliosis"],"prefix":"10.1155","volume":"2023","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6967-5426","authenticated-orcid":true,"given":"Parker","family":"Wengryn","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, University of Alberta, 8-39 Medical Sciences Building 8614-114 Street, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9114-9481","authenticated-orcid":true,"given":"Karina da Costa","family":"Silveira","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Alberta, 8-39 Medical Sciences Building 8614-114 Street, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7221-1187","authenticated-orcid":true,"given":"Connor","family":"Oborn","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Alberta, 8-39 Medical Sciences Building 8614-114 Street, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1459-3227","authenticated-orcid":true,"given":"Carrie-Lynn","family":"Soltys","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Alberta, 8-39 Medical Sciences Building 8614-114 Street, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9050-6061","authenticated-orcid":true,"given":"Alexander","family":"Beke","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Alberta, 8-39 Medical Sciences Building 8614-114 Street, Edmonton, Alberta, Canada"},{"name":"Department of Medicine, University of Alberta, Edmonton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9482-8647","authenticated-orcid":true,"given":"Inara","family":"Chacon-Fonseca","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Toronto, Toronto, Canada"},{"name":"Lakeridge Health Oshawa, Oshawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2673-7612","authenticated-orcid":true,"given":"Nadirah","family":"Damseh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6520-4096","authenticated-orcid":true,"given":"Marco Quesada","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Medical Genetics and Metabolics, Hospital Nacional de Ni\u00f1os, San Jos\u00e9, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9209-1779","authenticated-orcid":true,"given":"Ramses","family":"Badilla-Porras","sequence":"additional","affiliation":[{"name":"Medical Genetics and Metabolics, Hospital Nacional de Ni\u00f1os, San Jos\u00e9, Costa Rica"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5655-9805","authenticated-orcid":true,"given":"Peter","family":"Kannu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of Alberta, 8-39 Medical Sciences Building 8614-114 Street, Edmonton, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.20.2644-b"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000001187"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2019.01.095"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.05.104"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181e9f120"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.3390\/jdb9010005"},{"key":"7","first-page":"50","article-title":"Development of the axial skeleton and intervertebral disc","volume-title":"Current Topics in Developmental Biology","author":"S. 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