Simmer, James PJames PSimmerZhang, HongHongZhangMoon, Sophie J HSophie J HMoonDonnelly, Lori A-JLori A-JDonnellyYUAN-LING LEESeymen, FigenFigenSeymenKoruyucu, MineMineKoruyucuChan, Hui-ChenHui-ChenChanLee, Kevin YKevin YLeeWu, SuweiSuweiWuHsiang, Chia-LanChia-LanHsiangTsai, Anthony T PAnthony T PTsaiSlayton, Rebecca LRebecca LSlaytonMorrow, MelissaMelissaMorrowSHIH-KAI WANGShields, Edward DEdward DShieldsHu, Jan C-CJan C-CHu2023-05-042023-05-042022-05-122073-4425https://scholars.lib.ntu.edu.tw/handle/123456789/630768Mutations 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.enDSPP mutations; Shields Classification; Single Molecule Real-Time (SMRT) DNA sequencing; dentin dysplasia; dentinogenesis imperfecta; enamel malformations; whole-exome sequencing (WES)[SDGs]SDG3journal article10.3390/genes13050858356272432-s2.0-85130627635WOS:000803357000001https://api.elsevier.com/content/abstract/scopus_id/85130627635