The Modified Shields Classification and 12 Families with Defined DSPP Mutations

Genes

Edward D. Shields¹  Sophie J. H. Moon²  Jan C.-C. Hu²  James P. Simmer²  Hong Zhang²  Shih-Kai Wang³  Lori A-J. Donnelly⁴  Melissa Morrow⁵  Rebecca L. Slayton⁶  Figen Seymen⁷  Mine Koruyucu⁸  Yuan-Ling Lee⁹  Hui-Chen Chan^1,10  Anthony T. P. Tsai^1,10  Kevin Y. Lee^1,10  Suwei Wu^1,10  Chia-Lan Hsiang^1,10 

[1] 2161 Pardee Road, Neebing, Ontario, CA P7L 0G7, Canada;Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA;Department of Dentistry, National Taiwan University School of Dentistry, No. 1, Changde St., Zhongzheng Dist., Taipei City 100, Taiwan;Department of Oral and Maxillofacial Surgery, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;Department of Orthodontic and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA;Department of Pediatric Dentistry, University of Washington School of Dentistry, 1959 NE Pacific St., B-307, Seattle, WA 98195, USA;Department of Pedodontics, Faculty of Dentistry, Altinbas University, Istanbul 34147, Turkey;Department of Pedodontics, Faculty of Dentistry, Istanbul University, Istanbul 34116, Turkey;Graduate Institute of Clinical Dentistry, National Taiwan University, No.1, Chang-de St., Zhongzheng Dist., Taipei City 100, Taiwan;Taipei Municipal WanFang Hospital, Xinglong Rd. 111, Taipei City 100, Taiwan;

关键词: dentinogenesis imperfecta;    Shields Classification;    DSPP mutations;    dentin dysplasia;    enamel malformations;    whole-exome sequencing (WES);   

DOI  :  10.3390/genes13050858

来源: DOAJ

【 摘 要 】

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′-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 DSPP 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 COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5′-DSPP mutations, and 3′-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′-Dspp or 3′-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-DSPP defects be diagnosed as DGI-III, while those with 3′-DSPP defects be diagnosed as DGI-II.

【 授权许可】

Unknown