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American Journal of Medical Genetics.... May 2022Osteogenesis imperfecta (OI) is a rare low-bone mass skeletal Mendelian disorder characterized by bone fragility leading to bone fractures, with deformities and stunted...
Osteogenesis imperfecta (OI) is a rare low-bone mass skeletal Mendelian disorder characterized by bone fragility leading to bone fractures, with deformities and stunted growth in the more severe phenotypes. Other common, nonskeletal findings include blue sclerae and dentinogenesis imperfecta. It is caused mainly by quantitative or structural defects in type I collagen, although dysregulation of different signaling pathways that play a role in bone morphogenesis has been described to be associated with a small fraction of individuals with OI. Recently, a homozygous variant in the translation start site of CCDC134, showing increased activation of the RAS/MAPK signaling pathway, has been reported in three families of Moroccan origin with a severe, deforming form of OI. We report on a 9-year-old Brazilian boy, harboring the same homozygous variant in CCDC134, also presenting severe bone involvement. This report contributes to the phenotypic delineation of this novel autosomal recessive form of OI, which presents with high prevalence of nonunion fractures considered rare events in OI in general. In addition, it expands the phenotype to include base skull anomalies, potentially leading to serious complications, as seen in severe forms of OI. A poor response to bisphosphonate therapy was observed in these individuals. As the variant in CCDC134 leads to dysregulation of the RAS/MAPK signaling pathway, drugs targeted to this pathway could be an alternative to achieve a better management of these individuals.
Topics: Bone and Bones; Collagen Type I; Fractures, Bone; Homozygote; Humans; Membrane Proteins; Osteogenesis Imperfecta; Phenotype
PubMed: 35019224
DOI: 10.1002/ajmg.a.62651 -
Journal of Pharmacy & Bioallied Sciences Nov 2021The purpose of this study was to determine the prevalence of developmental dental anomalies in the East Indian subpopulation.
AIM
The purpose of this study was to determine the prevalence of developmental dental anomalies in the East Indian subpopulation.
MATERIALS AND METHODS
The study was based on clinical examination, evaluation of dental casts, and radiographs of 2385 Indian patients (1169 males and 1216 females), who visited Dental Institute, Rajendra Institute of Medical Sciences, Ranchi. These patients were examined for shape anomalies, number anomalies, structural anomalies, and positional anomalies.
RESULTS
It was observed that 5.83% of patients reported with a dental anomaly. Males reported with higher incidence with a male-to-female ratio of 1: 0.96. Microdontia was the most common anomaly. Unilateral microdontia was more common than bilateral and was more prominent in males (9.05%). It was observed that peg laterals were frequently encountered developmental anomaly at 1.34%, while the incidence of amelogenesis imperfecta and dentinogenesis imperfecta was 0.29% and 0.33%, respectively. The present demography reported a very low incidence of dens, fusion, hyperdontia, hypodontia, and macrodontia at <0.01%, whereas anomalies such as transportation, transmigration, and hypodontia of the maxillary molar reported no prevalence.
CONCLUSION
The percentage of dental anomalies although low should be treated as soon as possible to avoid further complications. The results of our study can serve as an indicator to ascertain the pattern of dental anomalies in Jharkhand. This might help to plan the dental treatment of the community.
PubMed: 35017914
DOI: 10.4103/jpbs.jpbs_148_21 -
Frontiers in Genetics 2021Bmp2 is essential for dentin development and formation. Bmp2 conditional knock-out (KO) mice display a similar tooth phenotype of dentinogenesis imperfecta (DGI). To...
Bmp2 is essential for dentin development and formation. Bmp2 conditional knock-out (KO) mice display a similar tooth phenotype of dentinogenesis imperfecta (DGI). To elucidate a foundation for subsequent functional studies of cross talk between mRNAs and lncRNAs in Bmp2-mediated dentinogenesis, we investigated the profiling of lncRNAs and mRNAs using immortalized mouse dental Bmp2 flox/flox (iBmp2) and Bmp2 knock-out (iBmp2) papilla cells. RNA sequencing was implemented to study the expression of the lncRNAs and mRNAs. Quantitative real-time PCR (RT-qPCR) was used to validate expressions of lncRNAs and mRNAs. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict functions of differentially expressed genes (DEGs). Protein-protein interaction (PPI) and lncRNA-mRNA co-expression network were analyzed by using bioinformatics methods. As a result, a total of 22 differentially expressed lncRNAs (16 downregulated vs 6 upregulated) and 227 differentially expressed mRNAs (133 downregulated vs. 94 upregulated) were identified in the iBmp2 cells compared with those of the iBmp2 cells. RT-qPCR results showed significantly differential expressions of several lncRNAs and mRNAs which were consistent with the RNA-seq data. GO and KEGG analyses showed differentially expressed genes were closely related to cell differentiation, transcriptional regulation, and developmentally relevant signaling pathways. Moreover, network-based bioinformatics analysis depicted the co-expression network between lncRNAs and mRNAs regulated by Bmp2 in mouse dental papilla cells and symmetrically analyzed the effect of Bmp2 during dentinogenesis via coding and non-coding RNA signaling.
PubMed: 35003201
DOI: 10.3389/fgene.2021.702540 -
Annals of Translational Medicine Nov 2021Dentinogenesis imperfecta (DGI), Shields type-II is an autosomal dominant genetic disease which severely affects the function of the patients' teeth. The dentin...
BACKGROUND
Dentinogenesis imperfecta (DGI), Shields type-II is an autosomal dominant genetic disease which severely affects the function of the patients' teeth. The dentin sialophosphoprotein () gene is considered to be the pathogenic gene of DGI-II. In this study, a DGI-II family with a novel DSPP mutation were collected, functional characteristics of DGI cells and clinical features were analyzed to better understand the genotype-phenotype relationship of this disease.
METHODS
Clinical data were collected, whole exome sequencing (WES) was conducted, and Sanger sequencing was used to verify the mutation sites. Physical characteristics of the patient's teeth were examined using scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). The localization of green fluorescent protein (GFP)-fused wild-type (WT) dentin sialoprotein (DSP) and its variant were evaluated via an immunocytochemistry (ICC) assay. The behaviors of human dental pulp stem cells (hDPSCs) were investigated by flow cytometry, osteogenic differentiation, and quantitative real-time polymerase chain reaction (qRT-PCR).
RESULTS
A novel heterozygous mutation c.53T > G (p. Val18Gly) in was found in this family. The SEM results showed that the participants' teeth had reduced and irregular dentinal tubes. The EDS results showed that the Ca/P ratio of the patients' teeth was significantly higher than that of the control group. The ICC assay showed that the mutant DSP was entrapped in the endoplasmic reticulum (ER), while the WT DSP located mainly in the Golgi apparatus. In comparison with normal cells, the patient's cells exhibited significantly decreased mineralization ability and lower expression levels of and .
CONCLUSIONS
The c.53T > G (p. Val18Gly) variant was shown to present with rare hypoplastic enamel defects. Functional analysis revealed that this novel variant disturbs dentinal characteristics and pulp cell behavior.
PubMed: 34988181
DOI: 10.21037/atm-21-5369 -
International Journal of Dentistry 2021Dentinogenesis imperfecta (DI) and amelogenesis imperfecta (AI) are hereditary abnormalities of dental hard tissues. Dental abnormalities may also be accompanied by... (Review)
Review
Dentinogenesis imperfecta (DI) and amelogenesis imperfecta (AI) are hereditary abnormalities of dental hard tissues. Dental abnormalities may also be accompanied by symptoms of disorders such as osteogenesis imperfecta. AI and DI have a significant burden on socializing, function, and comfort; therefore, frequent screening and accurate diagnosis is the cornerstone of managing such conditions. Both AI and DI could be treated with many strategies, including restorative, prosthetic, periodontal, surgical, and orthodontics treatment. The interdisciplinary combination of orthodontic, prosthodontic, and periodontic treatment has been proven to improve the prognosis of AI and DI. Regarding orthodontic treatment, the most difficult element of orthodontic therapy may be maintaining a high level of motivation for what might be a prolonged form of treatment spanning several years. There are many forms of orthodontic management for AI and DI, including removable appliances, functional appliances, and fixed appliances. Clear aligner therapy (CAT) contains a broad range of equipment that works in different ways, has different construction processes, and is compatible with different malocclusion procedures. The application of CAT in patients with AI and DI is favorable over the fixed applicants. However, the available evidence regarding the application of CAT in AI is weak and heterogeneous. In this review, we discussed the current evidence regarding the application of clear CAT in patients with AI and DI.
PubMed: 34976063
DOI: 10.1155/2021/7343094 -
Molecular Syndromology Oct 2021We report on 2 cousins, a girl and a boy, born to first-cousin Lebanese parents with Hamamy syndrome, exhibiting developmental delay, intellectual disability, severe...
We report on 2 cousins, a girl and a boy, born to first-cousin Lebanese parents with Hamamy syndrome, exhibiting developmental delay, intellectual disability, severe telecanthus, abnormal ears, dentinogenesis imperfecta, and bone fragility. Whole-exome sequencing studies performed on the 2 affected individuals and one obligate carrier revealed the presence of a homozygous c.503G>A (p.Arg168His) missense mutation in in both sibs, not reported in any other family. Review of the literature and differential diagnoses are discussed.
PubMed: 34899143
DOI: 10.1159/000517253 -
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 -
European Archives of Paediatric... Apr 2022Osteogenesis imperfecta (OI) results from mutations in the genes involved in the modification or biosynthesis of collagen. This study aimed to assess the oral...
PURPOSE
Osteogenesis imperfecta (OI) results from mutations in the genes involved in the modification or biosynthesis of collagen. This study aimed to assess the oral health-related quality of life (OHRQoL) in children with OI.
METHODOLOGY
Participants were recruited from a highly specialised OI centre for children. The Child Oral-Health Impact Profile-Short Form (COHIP-SF) was used, adding demographic and qualitative questions. Children aged 8-16 years participated between January and October 2019. Statistical analysis was carried out. A higher COHIP-SF score indicates better OHRQoL (maximum score, 76).
RESULTS
One hundred and six (106) children participated (44 female, mean age 11.93 years). COHIP-SF median score was 59. Children reporting mild OI (n = 55) had higher median scores (62) compared to severe OI (n = 7) with median scores of 55 (P = 0.087). When comparing mixed (< 12 years, n = 46) and permanent dentition (≥ 12, n = 60), no significant difference in OHRQoL was seen (P = 0.977). There was no significant difference between severities for each COHIP-SF domain. Limited data on the presence of dentinogenesis imperfecta did not impact overall score (P = 0.109), but was significant in the oral-health domain (P = 0.033).
QUALITATIVE
Common themes were the need for braces, discolouration, pain and function.
CONCLUSION
This study confirmed that children with OI have dental concerns in areas including oral health, functional well-being and socio-emotional well-being. This was related to severity of OI.
Topics: Child; Dentition, Permanent; Female; Humans; Oral Health; Osteogenesis Imperfecta; Quality of Life; Surveys and Questionnaires
PubMed: 34799841
DOI: 10.1007/s40368-021-00664-9 -
General Dentistry 2021Dentinogenesis imperfecta type 2, also referred to as Capdepont teeth and hereditary opalescent dentin, is a rare hereditary dysplasia affecting the dentin that occurs...
Dentinogenesis imperfecta type 2, also referred to as Capdepont teeth and hereditary opalescent dentin, is a rare hereditary dysplasia affecting the dentin that occurs during the histodifferentiation stage of tooth development. The resulting brownish gray opalescent hue creates an unesthetic appearance. This form of dentin anomaly occurs in approximately 1 in 8000 individuals in the United States. Teeth affected by hereditary dentin dysplasia chip easily, even under normal masticatory forces; however, as a result of underlying sclerotic dentin formation and obliteration of pulp chambers in response to attrition, these teeth are not hypersensitive. This case report describes this rare anomaly in a 27-year-old woman, whose discolored teeth were restored with ceramic laminate veneers.
Topics: Adult; Ceramics; Dentin; Dentinogenesis Imperfecta; Female; Humans; Tooth
PubMed: 34678748
DOI: No ID Found -
Calcified Tissue International Mar 2022Patients with Osteogenesis Imperfecta (OI) present extra-skeletal manifestations, including important orodental and craniofacial features as dentinogenesis imperfecta,...
Patients with Osteogenesis Imperfecta (OI) present extra-skeletal manifestations, including important orodental and craniofacial features as dentinogenesis imperfecta, dental agenesis, failure of maxilla growth and hypotonia of masticatory muscles. These features may compromise vital functions speech and mastication. Studies have demonstrated that cyclic pamidronate infusion, the standard therapy for patients with moderate to severe OI, influences the histomorphometric pattern of different body bones. The present study aimed to investigate the condyle trabecular bone pattern in OI patients. We used fractal dimension (FD) analysis on dental panoramic radiographic images to characterize the mandibular condyle trabecular bone in adolescents diagnosed with OI and treated with pamidronate. Imaging exam of 33 adolescents of both sexes, aged between 12 and 17 years, were analyzed and compared with 99 age- and sex-matched healthy adolescents. FD in patients was significantly lower (1.23 ± 0.15) than in healthy controls (1.29 ± 0.11; p < 0.01). Type of OI, age at treatment onset, and the duration of therapy were variables that showed a statistically significant effect on the FD results. This study demonstrated that the bone architecture of mandibular condyles may be altered in pediatric patients with moderate and severe forms of OI. Also, pamidronate treatment seems to have a positive effect on condyle trabecular bone in these patients. This is supported by our finding that FD values were positively influenced by the length of cyclic pamidronate treatment at the time of imaging, as well as by the age of the individual at treatment onset.
Topics: Adolescent; Bone Density; Cancellous Bone; Child; Diphosphonates; Female; Humans; Male; Mandibular Condyle; Osteogenesis Imperfecta; Pamidronate
PubMed: 34677656
DOI: 10.1007/s00223-021-00915-3