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The Chinese Journal of Dental Research Mar 2024The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3... (Review)
Review
The dentine sialophosphoprotein (DSPP) gene is the only identified causative gene for dentinogenesis imperfecta type 2 (DGI-II), dentinogenesis imperfecta type 3 (DGI-III) and dentine dysplasia type 2 (DD-II). These three disorders may have similar molecular mechanisms involved in bridging the DSPP mutations and the resulting abnormal dentine mineralisation. The DSPP encoding proteins DSP (dentine sialoprotein) and DPP (dentine phosphoprotein) are positive regulators of dentine formation and perform a function during dentinogenesis. The present review focused on the recent findings and viewpoints regarding the relationship between DSPP and dentinogenesis as well as mineralisation from multiple perspectives, involving studies relating to spatial structure and tissue localisation of DSPP, DSP and DPP, the biochemical characteristics and biological function of these molecules, and the causative role of the proteins in phenotypes of the knockout mouse model and in hereditary dentine defects.
Topics: Animals; Mice; Calcification, Physiologic; Calcinosis; Dentin; Dentinogenesis Imperfecta; Disease Models, Animal; Mice, Knockout; Humans; Sialoglycoproteins; Phosphoproteins
PubMed: 38546516
DOI: 10.3290/j.cjdr.b5136791 -
Journal of Oral and Maxillofacial... Mar 2021Dentinogenesis imperfecta (DGI) type II affects both primary and permanent dentitions and has the autosomal mode of inheritance. The affected teeth may appear as amber...
Dentinogenesis imperfecta (DGI) type II affects both primary and permanent dentitions and has the autosomal mode of inheritance. The affected teeth may appear as amber or gray because of chipping of enamel shortly after their eruption. Correct diagnosis and management are highly needed to restore the quality of oral health and to improve esthetics and masticatory functions. We present here a case of systematic and conservative dental approach in the management of a 7-year-old child having Dentinogenesis Imperfecta Type II (DGI Type II) with 1 ½ follow-up.
PubMed: 34083977
DOI: 10.4103/jomfp.JOMFP_172_20 -
Acta Medica Academica Aug 2021The aim of this paper is to describe the varying clinical and imaging manifestations of Osteogenesis Imperfecta (OI) in the fetus, the child, and the adult. OI is a...
The aim of this paper is to describe the varying clinical and imaging manifestations of Osteogenesis Imperfecta (OI) in the fetus, the child, and the adult. OI is a genetic disorder with mutation of Type 1 and non-type 1 collagen genes that results in disruption of multiple collagen based organ systems, most notably bones, often leading to "brittle bones". Additional features such as blue sclera, dentinogenesis imperfecta, joint and ligamentous hyperlaxity, hearing loss and cardiac defects may be present. Currently, there are at least 30 recognized genetic forms of OI. Given the multiple genes involved, variable genetic inheritance, and the wide range in phenotype, diagnosis can be challenging. While OI may sometimes be diagnosed in the fetus, patients with mild forms of OI may be diagnosed in childhood or even in adulthood. Imaging, including ultrasound, radiography, computed tomography, and magnetic resonance imaging, plays an important role in the diagnoses of OI in the fetus, the child, and the adult. Imaging is also crucial in identifying the many multisystem manifestations of OI. In particular, imaging can help differentiate manifestations of OI from injuries sustained in non-accidental trauma. Age, severity and manner of presentation of OI vary broadly depending on the specific genetic mutation involved, mode of inheritance, and age of the patient. Successful diagnosis of OI hinges on a detailed knowledge of the variable presentation and complications that may be encountered with this disease. CONCLUSION: In conclusion, OI comprises a heterogeneous group of genetic disorders responsible for bone fragility and additional connective tissue disorders, which can result in specific clinical and imaging findings in the fetus, the child, and the adult.
Topics: Adult; Fetus; Humans; Joint Instability; Mutation; Osteogenesis Imperfecta; Radiography
PubMed: 34847680
DOI: 10.5644/ama2006-124.343 -
Joint Bone Spine Oct 2019Osteogenesis imperfecta (OI) is a genetic disease whose clinical phenotype and severity vary considerably. The increased risk of fractures due to bone fragility persists... (Review)
Review
Osteogenesis imperfecta (OI) is a genetic disease whose clinical phenotype and severity vary considerably. The increased risk of fractures due to bone fragility persists in adulthood, notably after 40 years of age, albeit at a lower level than during growth. Adults with OI require periodic evaluations of the other manifestations of OI including hearing loss, respiratory impairments, ocular and dental abnormalities, and cardiovascular disease. Follow-up should therefore be provided by a multidisciplinary team, at intervals tailored to disease severity. Currently used treatments for OI have not been proven to decrease the fracture risk but are consistently effective in increasing bone mineral density. Specific orthopedic expertise is often required to treat fractures in patients with OI. A combination of periodic evaluations, chronic pain control, and disability management is necessary to improve quality of life.
Topics: Adult; Bone Density Conservation Agents; Diphosphonates; Disease Management; Humans; Orthopedic Procedures; Osteogenesis Imperfecta; Physical Therapy Modalities; Quality of Life
PubMed: 30742929
DOI: 10.1016/j.jbspin.2019.02.001 -
BMC Musculoskeletal Disorders Jan 2020Osteogenesis Imperfecta (OI) is characterized by bone fragility, and features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity and short...
BACKGROUND
Osteogenesis Imperfecta (OI) is characterized by bone fragility, and features such as blue sclerae, dentinogenesis imperfecta, hearing loss, ligamentous laxity and short stature can be present. It has long been assumed that the functional ability and quality of life of patients with OI depends primarily on the severity of skeletal deformities. However, fatigue is often mentioned in clinic by patients with all types of OI as an important modifier of their quality of life and does not always seem to be related to their functional ability. The aim of this study is to investigate whether adults with Osteogenesis Imperfecta are significantly more fatigued than the normal population.
METHODS
The Fatigue Severity Scale (FSS) was distributed by mobile phone application among 151 adult patients with different OI types. Results of the FSS in the OI group were compared with two control populations from America (n = 20) and the Netherlands (n = 113).
RESULTS
Ninety-nine patients (OI type 1 (n = 72), OI type 3 (n = 13), OI type 4 (n = 14) completed the FSS questionnaire. The mean FSS score of this cohort was 4.4 and significantly higher than the control populations (2.3/2.9). 65% of our cohort reported at least moderate fatigue compared with 2 control populations from America and the Netherlands.
CONCLUSION
Fatigue in patients with OI is a frequently encountered problem in our expert clinic but research into this topic is sparse. This pilot study is the largest study to date investigating fatigue in patients with OI and results have been compared with two control groups. The mean FSS score of 4.4 in the OI group indicates that people with OI are generally significantly more fatigued than the control population. Further evaluation of fatigue and its influencers in a larger group of OI patients is important for future management.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Phone; Cost of Illness; Cross-Sectional Studies; Fatigue; Female; Health Status; Humans; Male; Middle Aged; Mobile Applications; Osteogenesis Imperfecta; Pilot Projects; Predictive Value of Tests; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Young Adult
PubMed: 31900144
DOI: 10.1186/s12891-019-3000-7 -
International Endodontic Journal Aug 2023Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel...
AIM
Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK) and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapulpal calcifications.
METHODOLOGY
Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control.
RESULTS
Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTC CA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly) and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20 and WNT10A. Enrichment analyses indicated overrepresentation of gene sets associated with BMP and SMAD signalling pathways. In contrast, GO terms related to inflammation and axon development were underrepresented. Among BMP signalling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4 and BMP6 were upregulated, while BMP antagonists GREM1, BMPER and VWC2 showed decreased expression in ERS dental pulp tissues.
CONCLUSIONS
Upregulation of BMP signalling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.
Topics: Humans; Nephrocalcinosis; Amelogenesis Imperfecta; Dental Pulp; Dental Enamel Proteins; Mutation; Calcinosis; Gene Expression Profiling; Carrier Proteins
PubMed: 37159186
DOI: 10.1111/iej.13928 -
Healthcare (Basel, Switzerland) Aug 2022Dentinogenesis imperfecta type I (DGI-I) is a hereditary alteration of dentin associated with osteogenesis imperfecta (OI). To describe and study the morphological...
Dentinogenesis imperfecta type I (DGI-I) is a hereditary alteration of dentin associated with osteogenesis imperfecta (OI). To describe and study the morphological characteristics of DGI-I with scanning electron microscopy (SEM). Twenty-five teeth from 17 individuals diagnosed with OI and 30 control samples were studied with SEM at the level of the enamel, dentin-enamel junction (DEJ) and four levels of the dentin, studying its relationship with clinical-radiographic alterations. The variables were analysed using Fisher's exact test, with a confidence level of 95% and asymptotic significance. OI teeth showed alterations in the prismatic structure in 56%, interruption of the union in the enamel and dentin in 64% and alterations in the tubular structure in all of the cases. There is a relationship between the severity of OI and the morphological alteration of the dentin in the superficial ( = 0.019) and pulpar dentin ( 0.004) regions. : Morphological alterations of the tooth structure are found in OI samples in the enamel, DEJ and dentin in all teeth regardless of the presence of clinical-radiographic alterations. Dentin structural anomalies and clinical dental alterations were observed more frequently in samples from subjects with a more severe phenotype of OI.
PubMed: 36011110
DOI: 10.3390/healthcare10081453 -
Zhonghua Kou Qiang Yi Xue Za Zhi =... May 2020Developmental disorders of dental hard tissues are important components of non-carious diseases, which mainly include amelogenesis imperfecta and hereditary dentin... (Review)
Review
Developmental disorders of dental hard tissues are important components of non-carious diseases, which mainly include amelogenesis imperfecta and hereditary dentin disorders with various subtypes. In the absence of effective intervention, these disorders would lead to tooth sensitivity, defects of tooth structure or even loss of tooth, affecting the masticatory function and facial aesthetic configuration. At present, many dental clinicians may not have sufficient understanding of the diseases, and it is urgent to pay attention to the diseases per se and the patients affected. Based on the summary of the current research progresses, this article focuses on the clinical classification, the disease phenotype and the pathogenesis of gene mutations, in order to provide reference and help for the dental clinicians as well as the patients.
Topics: Amelogenesis Imperfecta; Dentin; Humans; Mutation; Tooth; Tooth Diseases
PubMed: 32392973
DOI: 10.3760/cma.j.cn112144-20200225-00086 -
Zhonghua Kou Qiang Yi Xue Za Zhi =... Aug 2023Dentin dysplasia type Ⅱ (DD-Ⅱ) is a subtype of hereditary dentin disorders. The dentin sialophosphoprotein (DSPP) gene has been revealed to be the causative gene,...
Dentin dysplasia type Ⅱ (DD-Ⅱ) is a subtype of hereditary dentin disorders. The dentin sialophosphoprotein (DSPP) gene has been revealed to be the causative gene, whose mutations could affect the normal tooth development process. The lesions involve both deciduous and permanent dentition, mainly manifested as tooth discoloration, attrition and even the subsequent malocclusion. If not treated in time, it will significantly affect the physical and psychological health of patients. The disease is difficult to be diagnosed in clinic accurately as its low incidence and hidden manifestations. The present article aims to discuss the clinical and radiographic characteristics, diagnosis, treatment of DD-Ⅱ, in order to improve the overall understanding on DD-Ⅱ for clinicians.
Topics: Humans; Dentin Dysplasia; Dentinogenesis Imperfecta; Sialoglycoproteins; Tooth; Mutation; Extracellular Matrix Proteins; Phosphoproteins; Dentin
PubMed: 37550036
DOI: 10.3760/cma.j.cn112144-20230410-00148 -
Calcified Tissue International May 2024Osteogenesis Imperfecta is a rare, hereditary bone condition with an incidence of 1/15,000-20,000. Symptoms include bone fragility, long bone deformity, scoliosis,... (Review)
Review
Osteogenesis Imperfecta is a rare, hereditary bone condition with an incidence of 1/15,000-20,000. Symptoms include bone fragility, long bone deformity, scoliosis, hypermobility, alongside secondary features such as short stature, basilar invagination, pulmonary and cardiac complications, hearing loss, dentinogenesis imperfecta and malocclusion. Osteogenesis Imperfecta can have a large impact on the child and their family; this impact starts immediately after diagnosis. Fractures, pain, immobility, hospital admissions and the need for equipment and adaptations all influence the health-related quality of life of the individual and their family. This narrative review article aims to examine the impact the diagnosis and management of osteogenesis imperfecta has on the health-related quality of life of a child. It will touch on the effect this may have on the quality of life of their wider family and friends and identify strategies to optimise health-related quality of life in this population. Optimising health-related quality of life in children with Osteogenesis Imperfecta is often a complicated, multifaceted journey that involves the child, their extended family, school, extracurricular staff and numerous health professionals.
PubMed: 38695871
DOI: 10.1007/s00223-024-01205-4