Dentinogenesis imperfecta type <scp>II</scp>‐ genotype and phenotype analyses in three Danish families

Taleb, Kawther; Lauridsen, Eva; Daugaard‐Jensen, Jette; Nieminen, Pekka; Kreiborg, Sven

doi:10.1002/mgg3.375

Cited by 15 publications

(23 citation statements)

References 31 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the enamel, calcium and phosphorus contents were significantly higher in the old age group than those in the young (He et al, 2011) while these correlations were not observed in the dentin (Fernández-Escudero et al, 2020). Previous studies reported that pulp chambers and root canals of DGI teeth were initially abnormally large and progressively obliterated due to irregular dentin deposition (Acevedo et al, 2009;Taleb et al, 2018). Consistently, DGI1, permanent tooth of the proband age 43, showed partially obliterated pulp cavities whereas DGI2, primary tooth of the proband son age 3, showed wide pulp cavity.…”

Section: Discussionmentioning

confidence: 87%

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

et al. 2020

View full text Add to dashboard Cite

Objectives: To investigate tooth ultrastructure and mutation of two patients in a family affected with osteogenesis imperfecta (OI) type IV and dentinogenesis imperfecta (DGI).Methods: Mutations were detected by whole exome and Sanger sequencing. The permanent second molar obtained from the proband (DGI1) and the primary first molar from his affected son (DGI2) were studied for their color, roughness, mineral density, hardness, elastic modulus, mineral content, and ultrastructure, compared to the controls.Results: Two novel missense COL1A2 variants, c.752C > T (p.Ser251Phe) and c.758G > T (p.Gly253Val), were identified in both patients. The c.758G > T was predicted to be the causative mutation. Pulp cavities of DGI1 (permanent teeth) were obliterated while those of DGI2 (primary teeth) were wide. The patients' teeth had darker and redder colors; reduced dentin hardness; decreased, disorganized, and scattered dentinal tubules and collagen fibers; and irregular dentinoenamel junction (DEJ), compared to controls. Lacunae-like structures were present in DGI2. Conclusions:We reported the novel causative mutation, c.758G > T (p.Gly253Val), in COL1A2 for OI type IV and DGI. The DGI dentin demonstrated inferior mechanical property and ultrastructure, suggesting severe disturbances of dentin formation.These could contribute to fragility and prone to infection of DGI teeth. This study expands phenotypic and genotypic spectra of COL1A2 mutations.

show abstract

Section: Discussionmentioning

confidence: 87%

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

et al. 2020

View full text Add to dashboard Cite

show abstract

“…At the present time the 19 different DSPP mutations that fall into the 5′ group are believed to affect trafficking of the DSPP protein. Direct effects on enamel have been demonstrated in the Brandywine isolate resulted from the DSPP p.(Pro17Ser) defect 39 , 43 . In addition, studies of patients with other 5′ DSPP mutations also demonstrated or suggested a direct enamel phenotype: p.(Pro17Leu) 17 , c.52-2A > G 43 , p.(Gln45His) 43 , and c.135 + 1G > A 14 .…”

Section: Discussionmentioning

confidence: 99%

Mouse Dspp frameshift model of human dentinogenesis imperfecta

Liang

Zhang

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Non-syndromic inherited defects of tooth dentin are caused by two classes of dominant negative/gain-of-function mutations in dentin sialophosphoprotein (DSPP): 5′ mutations affecting an N-terminal targeting sequence and 3′ mutations that shift translation into the − 1 reading frame. DSPP defects cause an overlapping spectrum of phenotypes classified as dentin dysplasia type II and dentinogenesis imperfecta types II and III. Using CRISPR/Cas9, we generated a Dspp−1fs mouse model by introducing a FLAG-tag followed by a single nucleotide deletion that translated 493 extraneous amino acids before termination. Developing incisors and/or molars from this mouse and a DsppP19L mouse were characterized by morphological assessment, bSEM, nanohardness testing, histological analysis, in situ hybridization and immunohistochemistry. DsppP19L dentin contained dentinal tubules but grew slowly and was softer and less mineralized than the wild-type. DsppP19L incisor enamel was softer than normal, while molar enamel showed reduced rod/interrod definition. Dspp−1fs dentin formation was analogous to reparative dentin: it lacked dentinal tubules, contained cellular debris, and was significantly softer and thinner than Dspp+/+ and DsppP19L dentin. The Dspp−1fs incisor enamel appeared normal and was comparable to the wild-type in hardness. We conclude that 5′ and 3′ Dspp mutations cause dental malformations through different pathological mechanisms and can be regarded as distinct disorders.

show abstract

“…It is generally believed that enamel readily chips off from the underlying defective dentin and/or abnormal DEJ after tooth eruption, thereby exposing the softer and malformed dentin to rapid attrition (Wright and Gantt, 1985;Kim et al, 2004;MacDougall et al, 2006;Hart and Hart, 2007;Kida et al, 2009;Min et al, 2014;Porntaveetus et al, 2018). However, it has also become evident that in some cases, the enamel itself may have intrinsic developmental defects (Lee et al, 2011;Wang et al, 2011;Bloch-Zupan et al, 2016;Taleb et al, 2018), which may be a direct contributing factor to rapid tooth wear observed in DGI patients. Consistently, we previously reported that both Dspp P19L/+ and Dspp P19L/P19L mice showed significantly reduced thickness of dental pulp chamber roof dentin and reduced dentin mineral densities (Liang et al, 2019), suggesting that the defective dentin may contribute to the accelerated tooth attrition as it cannot provide adequate support to the overlying enamel.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Dspp ablation in mice causes a defective dentin mineralization, resulting in a tooth phenotype similar to that observed in human DGI type III patients (Sreenath et al, 2003). In addition to dentin, enamel formation may be affected by DSPP mutations in DGI patients (Lee et al, 2011;Wang et al, 2011;Bloch-Zupan et al, 2016;Taleb et al, 2018). However, very limited studies have been done to understand how mutant DSPP proteins interfere with amelogenesis to date.…”

Section: Introductionmentioning

confidence: 86%

Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice

Liang

Zhang

et al. 2021

Front. Physiol.

View full text Add to dashboard Cite

Dentin sialophosphoprotein (DSPP) is an extracellular matrix protein that is highly expressed in odontoblasts, but only transiently expressed in presecretory ameloblasts during tooth development. We previously generated a knockin mouse model expressing a mouse equivalent (DSPP, p.P19L) of human mutant DSPP (p.P17L; referred to as “DsppP19L/+”), and reported that DsppP19L/+ and DsppP19L/P19L mice manifested a dentin phenotype resembling human dentinogenesis imperfecta (DGI). In this study, we analyzed pathogenic effects of mutant P19L-DSPP on enamel development in DsppP19L/+ and DsppP19L/P19L mice. Micro-Computed Tomography (μCT) analyses of 7-week-old mouse mandibular incisors showed that DsppP19L/P19L mice had significantly decreased enamel volume and/or enamel density at different stages of amelogenesis examined. Acid-etched scanning electron microscopy (SEM) analyses of mouse incisors demonstrated that, at the mid-late maturation stage of amelogenesis, the enamel of wild-type mice already had apparent decussating pattern of enamel rods, whereas only minute particulates were found in DsppP19L/+ mice, and no discernible structures in DsppP19L/P19L mouse enamel. However, by the time that incisor enamel was about to erupt into oral cavity, distinct decussating enamel rods were evident in DsppP19L/+ mice, but only poorly-defined enamel rods were revealed in DsppP19L/P19L mice. Moreover, μCT analyses of the mandibular first molars showed that DsppP19L/+ and DsppP19L/P19L mice had a significant reduction in enamel volume and enamel density at the ages of 2, 3, and 24weeks after birth. Backscattered and acid-etched SEM analyses revealed that while 3-week-old DsppP19L/+ mice had similar pattern of enamel rods in the mandibular first molars as age-matched wild-type mice, no distinct enamel rods were observed in DsppP19L/P19L mice. Yet neither DsppP19L/+ nor DsppP19L/P19L mice showed well-defined enamel rods in the mandibular first molars by the age of 24weeks, as judged by backscattered and acid-etched SEM. In situ hybridization showed that DSPP mRNA level was markedly reduced in the presecretory ameloblasts, but immunohistochemistry revealed that DSP/DSPP immunostaining signals were much stronger within the presecretory ameloblasts in Dspp mutant mice than in wild-type mice. These results suggest that mutant P19L-DSPP protein caused developmental enamel defects in mice, which may be associated with intracellular retention of mutant DSPP in the presecretory ameloblasts.

show abstract

Dentinogenesis imperfecta type II‐ genotype and phenotype analyses in three Danish families

Cited by 15 publications

References 31 publications

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

Tooth ultrastructure of a novel COL1A2 mutation expanding its genotypic and phenotypic spectra

Mouse Dspp frameshift model of human dentinogenesis imperfecta

Enamel Defects Associated With Dentin Sialophosphoprotein Mutation in Mice

Contact Info

Product

Resources

About