{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:18:55Z","timestamp":1773386335687,"version":"3.50.1"},"reference-count":101,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["DE027675"],"award-info":[{"award-number":["DE027675"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["107-N3966"],"award-info":[{"award-number":["107-N3966"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["108-2314-B-002-038-MY3"],"award-info":[{"award-number":["108-2314-B-002-038-MY3"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Taiwan University Hospital (NTUH)","award":["DE027675"],"award-info":[{"award-number":["DE027675"]}]},{"name":"National Taiwan University Hospital (NTUH)","award":["107-N3966"],"award-info":[{"award-number":["107-N3966"]}]},{"name":"National Taiwan University Hospital (NTUH)","award":["108-2314-B-002-038-MY3"],"award-info":[{"award-number":["108-2314-B-002-038-MY3"]}]},{"name":"Ministry of Science and Technology in Taiwan (MOST)","award":["DE027675"],"award-info":[{"award-number":["DE027675"]}]},{"name":"Ministry of Science and Technology in Taiwan (MOST)","award":["107-N3966"],"award-info":[{"award-number":["107-N3966"]}]},{"name":"Ministry of Science and Technology in Taiwan (MOST)","award":["108-2314-B-002-038-MY3"],"award-info":[{"award-number":["108-2314-B-002-038-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentinogenesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5\u2032-group that affects protein targeting and a 3\u2032-group that shifts translation into the \u22121 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T&gt;C\/p.(Val18Ala); c.3461delG\/p.(Ser1154Metfs*160); and c.3700delA\/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5\u2032-DSPP mutations, and 3\u2032-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5\u2032-Dspp or 3\u2032-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5\u2032-DSPP defects be diagnosed as DGI-III, while those with 3\u2032-DSPP defects be diagnosed as DGI-II.<\/jats:p>","DOI":"10.3390\/genes13050858","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T03:28:43Z","timestamp":1652326123000},"page":"858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Modified Shields Classification and 12 Families with Defined DSPP Mutations"],"prefix":"10.3390","volume":"13","author":[{"given":"James P.","family":"Simmer","sequence":"first","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4558-9026","authenticated-orcid":false,"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie J. H.","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-8842","authenticated-orcid":false,"given":"Lori A-J.","family":"Donnelly","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan-Ling","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Dentistry, National Taiwan University, No.1, Chang-de St., Zhongzheng Dist., Taipei City 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Figen","family":"Seymen","sequence":"additional","affiliation":[{"name":"Department of Pedodontics, Faculty of Dentistry, Altinbas University, Istanbul 34147, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2077-5095","authenticated-orcid":false,"given":"Mine","family":"Koruyucu","sequence":"additional","affiliation":[{"name":"Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34116, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui-Chen","family":"Chan","sequence":"additional","affiliation":[{"name":"Taipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin Y.","family":"Lee","sequence":"additional","affiliation":[{"name":"Taipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Taipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Lan","family":"Hsiang","sequence":"additional","affiliation":[{"name":"Taipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony T. P.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Taipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca L.","family":"Slayton","sequence":"additional","affiliation":[{"name":"Department of Pediatric Dentistry, University of Washington School of Dentistry, 1959 NE Pacific St., B-307, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Orthodontic and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8378-5880","authenticated-orcid":false,"given":"Shih-Kai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dentistry, National Taiwan University School of Dentistry, No. 1, Changde St., Zhongzheng Dist., Taipei City 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward D.","family":"Shields","sequence":"additional","affiliation":[{"name":"2161 Pardee Road, Neebing, Ontario, CA P7L 0G7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9294-0248","authenticated-orcid":false,"given":"Jan C.-C.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"711","DOI":"10.2741\/e281","article-title":"Dentin: Structure, composition and mineralization","volume":"3","author":"Goldberg","year":"2011","journal-title":"Front Biosci. 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