The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> Mutations
Mutations in Dentin Sialophosphoprotein (<i>DSPP</i>) 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). <i>DSPP</i> mutations fall into two group...
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MDPI AG
2022-05-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/5/858 |
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| author | James P. Simmer Hong Zhang Sophie J. H. Moon Lori A-J. Donnelly Yuan-Ling Lee Figen Seymen Mine Koruyucu Hui-Chen Chan Kevin Y. Lee Suwei Wu Chia-Lan Hsiang Anthony T. P. Tsai Rebecca L. Slayton Melissa Morrow Shih-Kai Wang Edward D. Shields Jan C.-C. Hu |
| author_facet | James P. Simmer Hong Zhang Sophie J. H. Moon Lori A-J. Donnelly Yuan-Ling Lee Figen Seymen Mine Koruyucu Hui-Chen Chan Kevin Y. Lee Suwei Wu Chia-Lan Hsiang Anthony T. P. Tsai Rebecca L. Slayton Melissa Morrow Shih-Kai Wang Edward D. Shields Jan C.-C. Hu |
| author_sort | James P. Simmer |
| collection | DOAJ |
| description | Mutations in Dentin Sialophosphoprotein (<i>DSPP</i>) 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). <i>DSPP</i> mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing <i>DSPP</i> mutations in 12 families. Three of the mutations are novel: c.53T>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 <i>COL1A1</i> and <i>COL1A2</i> causing dominant forms of osteogenesis imperfecta, 5′-<i>DSPP</i> mutations, and 3′-<i>DSPP</i> frameshifts near the margins of the <i>DSPP</i> 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′-<i>Dspp</i> or 3′-<i>Dspp</i> mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-<i>DSPP</i> defects be diagnosed as DGI-III, while those with 3′-<i>DSPP</i> defects be diagnosed as DGI-II. |
| first_indexed | 2024-03-10T03:49:34Z |
| format | Article |
| id | doaj.art-b20debd90ff74382b3797846fb3608b5 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T03:49:34Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-b20debd90ff74382b3797846fb3608b52023-11-23T11:10:35ZengMDPI AGGenes2073-44252022-05-0113585810.3390/genes13050858The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> MutationsJames P. Simmer0Hong Zhang1Sophie J. H. Moon2Lori A-J. Donnelly3Yuan-Ling Lee4Figen Seymen5Mine Koruyucu6Hui-Chen Chan7Kevin Y. Lee8Suwei Wu9Chia-Lan Hsiang10Anthony T. P. Tsai11Rebecca L. Slayton12Melissa Morrow13Shih-Kai Wang14Edward D. Shields15Jan C.-C. Hu16Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USADepartment of Oral and Maxillofacial Surgery, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USAGraduate Institute of Clinical Dentistry, National Taiwan University, No.1, Chang-de St., Zhongzheng Dist., Taipei City 100, TaiwanDepartment of Pedodontics, Faculty of Dentistry, Altinbas University, Istanbul 34147, TurkeyDepartment of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34116, TurkeyTaipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, TaiwanTaipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, TaiwanTaipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, TaiwanTaipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, TaiwanTaipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, TaiwanDepartment of Pediatric Dentistry, University of Washington School of Dentistry, 1959 NE Pacific St., B-307, Seattle, WA 98195, USADepartment of Orthodontic and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USADepartment of Dentistry, National Taiwan University School of Dentistry, No. 1, Changde St., Zhongzheng Dist., Taipei City 100, Taiwan2161 Pardee Road, Neebing, Ontario, CA P7L 0G7, CanadaDepartment of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USAMutations in Dentin Sialophosphoprotein (<i>DSPP</i>) 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). <i>DSPP</i> mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing <i>DSPP</i> mutations in 12 families. Three of the mutations are novel: c.53T>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 <i>COL1A1</i> and <i>COL1A2</i> causing dominant forms of osteogenesis imperfecta, 5′-<i>DSPP</i> mutations, and 3′-<i>DSPP</i> frameshifts near the margins of the <i>DSPP</i> 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′-<i>Dspp</i> or 3′-<i>Dspp</i> mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-<i>DSPP</i> defects be diagnosed as DGI-III, while those with 3′-<i>DSPP</i> defects be diagnosed as DGI-II.https://www.mdpi.com/2073-4425/13/5/858dentinogenesis imperfectaShields Classification<i>DSPP</i> mutationsdentin dysplasiaenamel malformationswhole-exome sequencing (WES) |
| spellingShingle | James P. Simmer Hong Zhang Sophie J. H. Moon Lori A-J. Donnelly Yuan-Ling Lee Figen Seymen Mine Koruyucu Hui-Chen Chan Kevin Y. Lee Suwei Wu Chia-Lan Hsiang Anthony T. P. Tsai Rebecca L. Slayton Melissa Morrow Shih-Kai Wang Edward D. Shields Jan C.-C. Hu The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> Mutations Genes dentinogenesis imperfecta Shields Classification <i>DSPP</i> mutations dentin dysplasia enamel malformations whole-exome sequencing (WES) |
| title | The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> Mutations |
| title_full | The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> Mutations |
| title_fullStr | The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> Mutations |
| title_full_unstemmed | The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> Mutations |
| title_short | The Modified Shields Classification and 12 Families with Defined <i>DSPP</i> Mutations |
| title_sort | modified shields classification and 12 families with defined i dspp i mutations |
| topic | dentinogenesis imperfecta Shields Classification <i>DSPP</i> mutations dentin dysplasia enamel malformations whole-exome sequencing (WES) |
| url | https://www.mdpi.com/2073-4425/13/5/858 |
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