{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:36:46Z","timestamp":1790501806623,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["093113"],"award-info":[{"award-number":["093113"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Astbury Centre for Structural Molecular Biology"},{"name":"Faculty of Biological Sciences","award":["062164\/Z00\/Z"],"award-info":[{"award-number":["062164\/Z00\/Z"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Amelogenesis is the process of enamel formation. For amelogenesis to proceed, the cells of the inner enamel epithelium (IEE) must first proliferate and then differentiate into the enamel-producing ameloblasts. Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective or absent tooth enamel. We identified a 2\u00a0bp variant c.817_818GC&amp;gt;AA in SP6, the gene encoding the SP6 transcription factor, in a Caucasian family with autosomal dominant hypoplastic AI. The resulting missense protein change, p.(Ala273Lys), is predicted to alter a DNA-binding residue in the first of three zinc fingers. SP6 has been shown to be crucial to both proliferation of the IEE and to its differentiation into ameloblasts. SP6 has also been implicated as an AI candidate gene through its study in rodent models. We investigated the effect of the missense variant in SP6 (p.(Ala273Lys)) using surface plasmon resonance protein-DNA binding studies. We identified a potential SP6 binding motif in the AMBN proximal promoter sequence and showed that wild-type (WT) SP6 binds more strongly to it than the mutant protein. We hypothesize that SP6 variants may be a very rare cause of AI due to the critical roles of SP6 in development and that the relatively mild effect of the missense variant identified in this study is sufficient to affect amelogenesis causing AI, but not so severe as to be incompatible with life. We suggest that current AI cohorts, both with autosomal recessive and dominant disease, be screened for SP6 variants.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa041","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T12:37:09Z","timestamp":1584016629000},"page":"1417-1425","source":"Crossref","is-referenced-by-count":24,"title":["A missense variant in specificity protein 6 (SP6) is associated with amelogenesis imperfecta"],"prefix":"10.1093","volume":"29","author":[{"given":"Claire E L","family":"Smith","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, Leeds Institute of Medical Research, Faculty of Medicine and Health, St James\u2019s University Hospital, University of Leeds, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L E","family":"Whitehouse","sequence":"first","affiliation":[{"name":"School of Dentistry, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9LU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A","family":"Poulter","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, Leeds Institute of Medical Research, Faculty of Medicine and Health, St James\u2019s University Hospital, University of Leeds, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Wilkinson Hewitt","sequence":"first","affiliation":[{"name":"Protein Production Facility, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Nadat","sequence":"first","affiliation":[{"name":"Protein Production Facility, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R","family":"Jackson","sequence":"first","affiliation":[{"name":"Protein Production Facility, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain W","family":"Manfield","sequence":"first","affiliation":[{"name":"Centre for Biomolecular Interactions Technology Facility, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A","family":"Edwards","sequence":"first","affiliation":[{"name":"School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen D","family":"Rodd","sequence":"first","affiliation":[{"name":"Academic Unit of Oral Health Dentistry and Society, School of Clinical Dentistry, University of Sheffield, Sheffield, S10 2TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris F","family":"Inglehearn","sequence":"first","affiliation":[{"name":"Division of Molecular Medicine, Leeds Institute of Medical Research, Faculty of Medicine and Health, St James\u2019s University Hospital, University of Leeds, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan J","family":"Mighell","sequence":"first","affiliation":[{"name":"School of Dentistry, Faculty of Medicine and Health, University of Leeds, Leeds LS2 9LU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"key":"2020060307000232900_ref1","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1177\/10454411980090020101","article-title":"Cellular and chemical events during enamel maturation","volume":"9","author":"Smith","year":"1998","journal-title":"Crit. 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