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Objective: This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the molecules involved, and related mechanisms. Subjects and Methods: References on genetic diseases with dentin malformations were obtained from various sources, including PubMed, OMIM, NCBI, and other websites. The clinical phenotypes and genetic backgrounds of these diseases were then summarized, analyzed, and compared. Results: Over 10 systemic diseases, including osteogenesis imperfecta, hypophosphatemic rickets, vitamin D‐dependent rickets, familial tumoral calcinosis, Ehlers‐Danlos syndrome, Schimke immuno‐osseous dysplasia, hypophosphatasia, Elsahy‐Waters syndrome, Singleton‐Merten syndrome, odontochondrodysplasia, and microcephalic osteodysplastic primordial dwarfism type II were examined. Most of these are bone disorders, and their pathogenic genes may regulate both dentin and bone development, involving extracellular matrix, cell differentiation, and metabolism of calcium, phosphorus, and vitamin D. The phenotypes of these syndromic dentin defects various with the involved genes, part of them are similar to dentinogenesis imperfecta or dentin dysplasia, while others only present one or two types of dentin abnormalities such as discoloration, irregular enlarged or obliterated pulp and canal, or root malformation. Conclusion: Some specific dentin defects associated with systemic diseases may serve as important phenotypes for dentists to diagnose. Furthermore, mechanistic studies on syndromic dentin defects may provide valuable insights into isolated dentin defects and general dentin development or mineralization. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the mutation in a Chinese family with dentin dysplasia type II (DD‐II) and to summarize mutation hotspots, clinical manifestations, and disease management strategies. Phenotype analysis, clinical intervention, mutation screening, and cosegregation analysis within the enrolled family were performed. A summary of the reported mutations in the dentin phosphoprotein (DPP) region of dentin sialophosphoprotein (DSPP) was analyzed. Pathogenicity prediction analysis of the physical properties and function of DSPP variants was performed by bioinformatic processing. Clinical management strategies are discussed. A novel pathogenic mutation (c.2035delA) in the DPP region of DSPP was identified, which was cosegregated in the family. The immature permanent teeth of patients with DD‐II presented with X‐shaped root canal phenotypes. Most of the identified mutations for DD‐II were clustered in the DPP region between nucleotides 1686–2134. Points of differential diagnosis, clinical interventions, and management strategies are proposed. This study revealed a novel DSPP frameshift mutation and presented new clinical features of DD‐II. The locus involving nucleotides 1686–2134 of DSPP may represent a mutational hotspot for the disease. Appropriate management of DD‐II at different stages is important to avoid the development of secondary dental lesions. [ABSTRACT FROM AUTHOR]

Hereditary dentin disorders include dentinogenesis imperfecta (DGI) and dentin dysplasia (DD), which are autosomal dominant diseases characterized by altered dentin structure such as abnormality in dentin mineralization and the absence of root dentin. Shields classified DGI into three subgroups and DD into two subtypes. Although they are all hereditary dentin diseases, they do not share the same causative genes. To date, the pathogenic genes of DGI type I, which is considered a clinical manifestation of syndrome osteogenesis imperfecta, include COL1A1 and COL1A2. Mutations of the DSPP gene, which encodes the dentin sialophosphoprotein, a major non‐collagenous protein, are responsible for three isolated dentinal diseases: DGI‐II, DGI‐III, and DD‐II. However, DD‐I appears to be special in that researchers have found three pathogenicity genes―VPS4B,SSUH2, and SMOC2―in three affected families from different countries. It is believed that DD‐I is a genetically heterogeneous disease and is distinguished from other types of dentin disorders. This review summarizes the DD‐I literature in the context of clinical appearances, radiographic characteristics, and functions of its pathogenic genes and aims to serve clinicians in further understanding and diagnosing this disease. [ABSTRACT FROM AUTHOR]

Objective Hereditary dentin defects can be categorised into two classes according to their clinical manifestations: dentinogenesis imperfecta ( DGI), which includes three types ( DGI-I, DGI- II and DGI- III), and dentin dysplasia ( DD), which includes two types ( DD-I and DD- II). This study investigated the phenotypic characteristics and genetic causes of hereditary dentin defects in seven Chinese families. Materials and methods Seven families affected with DGI- II, DGI- III or DD- II were enrolled. Clinical examinations were performed to determine the phenotypic characteristics, and DNA samples were collected for Sanger sequencing. Results Clinical diagnoses revealed DGI- II in five families, DGI- III in one family and DD- II in one family. Variants of the dentin sialophosphoprotein ( DSPP) gene were found in six of the seven families. Of these, c.52G>T was identified in two families. Each of the remaining four families had a different variant: c.2684delG, c.52-2A>G, c.1874-1877del ACAG and c.3509-3521del13bp; the last three variants were novel. Conclusions This is the first study to analyse all three important types of hereditary dentin defect and include comprehensive genetic analyses of both dentin sialoprotein and dentin phosphoprotein in Chinese families. This study expands the spectrum of DSPP variants, highlighting their associated phenotypic continuum. [ABSTRACT FROM AUTHOR]

Dentinogenesis imperfecta and dentin dysplasia are two common types of genetic oral diseases resulted from the aberrant differentiation of odontoblast. Understanding the mechanisms of odontoblast differentiation is crucial for finding the diagnosis candidate genes and treatment targets for such kinds of diseases. Previous work has identified a battery of transcription factors and growth factors regulating odontoblast differentiation; however, the post-transcriptional regulating mechanisms of them are poorly studied. Micro RNAs (mi RNA) are a group of non-coding RNAs widely studied in organ development, inflammation, and tumorigenesis because of its inhibitory effects on the target m RNAs. Also, mi RNAs along with their binding targets form a complex competing endogenous RNA (ce RNA) network where mi RNAs serve as the fine tuning balancers between their targets. Recent reports demonstrated the essential role of the mi RNA pathway in dentinogenesis and the regulatory role of several specific mi RNAs in the in vitro model of odontoblast differentiation. Herein, we will discuss the general roles of mi RNA in diseases, the function of mi RNAs during odontoblast differentiation, and finally the potential pathological mechanisms through which mi RNAs cause the odontoblast-related diseases. [ABSTRACT FROM AUTHOR]

Oral Diseases (2011) 17, 690-695 Objective: Dentin sialophosphoprotein ( DSPP) gene mutations have been identified in isolated hereditary dentin defects; however, the genotype-phenotype correlations are poorly understood. We performed in vitro splicing assays to test the hypothesis that DSPP mutations in splice junctions as well as proposed missense/nonsense mutations experimentally result in aberrant pre-mRNA splicing. Materials and methods: The genomic fragment of the human DSPP gene was cloned into the pSPL3 splicing vector, and previously reported as well as informative de novo mutations were then introduced by PCR mutagenesis. The COS-7 cells were transfected with each plasmid vector, and total RNA was isolated. RT-PCR result was analyzed, and the band intensity of the product was calibrated using ImageJ. Results: The predictions by others of exon 3 skipping in specific DSPP mutations have been validated and a cryptic splicing donor site has been identified. However, the degree of mutational effect on pre-mRNA splicing varied considerably depending on the changed nucleotide. Conclusions: The predictions of exon 3 skipping in specific DSPP mutations have been validated, and a cryptic splicing donor site has been identified. Our data may provide insight into the contribution of DSPP mutations in the pathogenesis and genotype-phenotype correlations of hereditary dentin defects. [ABSTRACT FROM AUTHOR]

Oral Diseases (2011) , 314-319 Hereditary dentin defects can be grouped into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia. Tooth enamel is considered normal in patients with hereditary dentin defects, but is easily worn down and fractured due to DSPP mutation-induced altered dentin properties. The purposes of this study were to identify genetic cause of a family with type II DGI and enamel defects. We identified a family with type II DGI and a unique form of hypoplastic enamel defect affecting occlusal third of the crown. Family members were recruited for the genetic analysis and DNA was obtained from peripheral whole blood. Mutational analysis revealed a T to A transversion in exon 3 of the DSPP (c.53T>A, p.V18D). Haplotype analysis showed that the same mutation arose separately in two different families having DGI with similar enamel defects, indicating that this phenotype is associated with this specific DSPP mutation. Clinical features suggest that enamel formation was affected in the affected individuals during early amelogenesis, in addition to the dentin defect. We observed that a DSPP gene mutation not only influences dentinogenesis but also affects early stage amelogenesis. [ABSTRACT FROM AUTHOR]