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International Immunology Mar 2021Mutations in DDX58 (DExD/H-box helicase 58), which encodes the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I), were recently identified in the rare...
Mutations in DDX58 (DExD/H-box helicase 58), which encodes the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I), were recently identified in the rare autoimmune disease Singleton-Merten syndrome (SMS). We report the spontaneous development of psoriasis-like skin lesions as an SMS-like symptom in transgenic mice harboring one of the RIG-I SMS variants, E373A. Histological analysis revealed typical characteristics of psoriasis, including the abnormal proliferation and differentiation of keratinocytes leading to epidermal hyperplasia, and infiltrates consisting of neutrophils, dendritic cells and T cells. Levels of the IL-23/IL-17 immune axis cytokines were high in the skin lesions. Rag2-/- transgenic mice showed partial amelioration of the phenotype, with down-regulation of inflammatory cytokines, including IL-17A, suggesting the importance of lymphocytes for the pathogenesis similar to that of human psoriasis. Of note, IL-17A deficiency abolished the skin phenotype, and treatment using the JAK inhibitor tofacitinib not only prevented onset, but also improved the skin manifestations even after onset. Our study provides further evidence for the involvement of RIG-I activation in the onset and progression of psoriasis via type I interferon signaling and the IL-23/IL-17 axis.
Topics: Animals; Aortic Diseases; DEAD Box Protein 58; DNA-Binding Proteins; Dendritic Cells; Dental Enamel Hypoplasia; Epidermis; Hyperplasia; Interferon Type I; Interleukin-17; Interleukin-23 Subunit p19; Janus Kinase Inhibitors; Janus Kinases; Keratinocytes; Metacarpus; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscular Diseases; Neutrophils; Odontodysplasia; Osteoporosis; Piperidines; Psoriasis; Pyrimidines; T-Lymphocytes; Vascular Calcification
PubMed: 33119735
DOI: 10.1093/intimm/dxaa071 -
Oral Health & Preventive Dentistry Sep 2020Regional odontodysplasia (RO) is a rare dental anomaly affecting primary and/or permanent dentition, and leads to comprehensive treatment need. The purpose of this study... (Review)
Review
PURPOSE
Regional odontodysplasia (RO) is a rare dental anomaly affecting primary and/or permanent dentition, and leads to comprehensive treatment need. The purpose of this study was to present a larger consecutive sample with RO, discuss treatment strategies for patients with RO, and review the literature.
MATERIALS AND METHODS
A consecutive, retrospective sample of seven children with RO (6 males, 1 female) including all patients diagnosed with RO in the eastern part of Denmark was conducted over a period of 15 years. The evaluation included gender, localisation and treatment outcome. A review of the literature and cases published within the last 15 years was conducted.
RESULT
Referral age was 2-12 years (mean: 7.3 years). The gender ratio was 1:6 (female:male), and the right:left ratio was 3:4. 71% of the patients had RO in the mandible and 29% in the maxilla. 43% had RO in the permanent dentition, while both primary and permanent dentition were affected in 57%. Typically, RO affected incisors and canines. In some patients, RO also affected more distal tooth types. Treatment included early multiple extractions and subsequent combined orthodontics, surgery and prosthetics. A search on RO cases published within the last 15 years was conducted and included 44 cases. The review showed a male and maxillary preponderance. The most common treatment of RO is extraction.
CONCLUSION
Treatment of RO should take place in interdisciplinary, specialised teams, and individual treatment plans should be designed. Fewer but more extensive treatment sessions under general anesthaesia may minimise the burden of care for the patients.
Topics: Child; Dentition, Permanent; Female; Humans; Incisor; Male; Mandible; Odontodysplasia; Retrospective Studies
PubMed: 32895649
DOI: 10.3290/j.ohpd.a45070 -
European Journal of Paediatric Dentistry Sep 2020Segmental odontomaxillary dysplasia is an uncommon nonhereditary growth disorder that affects the maxilla, gums and ipsilateral dentition. The disorder is diagnosed...
BACKGROUND
Segmental odontomaxillary dysplasia is an uncommon nonhereditary growth disorder that affects the maxilla, gums and ipsilateral dentition. The disorder is diagnosed mainly based on dental (over-retention of primary teeth, dental agenesis and diastemas) and bone findings (bone sclerosis, irregular trabeculation of immature bone and reduced maxillary sinus). This paper provides a case report.
CASE REPORT
A 5-year-old child with skin manifestations including hypertrichosis, facial erythema and pigmented nevus was diagnosed with type II segmental odontomaxillary dysplasia based on clinical, radiographic and histopathological analysis.
CONCLUSION
The skin findings can help with the suspicion of segmental odontomaxillary dysplasia, although the definitive diagnosis is typically established by a paediatric dentist based on clinical and radiological findings.
Topics: Child, Preschool; Diastema; Humans; Maxilla; Odontodysplasia; Skin Diseases; Tooth, Deciduous
PubMed: 32893658
DOI: 10.23804/ejpd.2020.21.03.14 -
Methods in Molecular Biology (Clifton,... 2021The type I interferonopathies comprise a heterogenous group of monogenic diseases associated with a constitutive activation of type I interferon signaling.The... (Review)
Review
The type I interferonopathies comprise a heterogenous group of monogenic diseases associated with a constitutive activation of type I interferon signaling.The elucidation of the genetic causes of this group of diseases revealed an alteration of nucleic acid processing and signaling.ADAR1 is among the genes found mutated in patients with this type of disorders.This enzyme catalyzes the hydrolytic deamination of adenosines in inosines within a double-stranded RNA target (RNA editing of A to I). This RNA modification is widespread in human cells and deregulated in a variety of human diseases, ranging from cancers to neurological abnormalities.In this review, we briefly summarize the knowledge about the RNA editing alterations occurring in patients with mutations in ADAR1 gene and how these alterations might cause the inappropriate IFN activation.
Topics: Adenosine Deaminase; Aortic Diseases; Autoimmune Diseases of the Nervous System; Dental Enamel Hypoplasia; Genetic Diseases, Inborn; Humans; Immunity, Innate; Interferon Type I; Metacarpus; Muscular Diseases; Nervous System Malformations; Odontodysplasia; Osteoporosis; RNA Editing; RNA, Double-Stranded; RNA-Binding Proteins; Signal Transduction; Vascular Calcification
PubMed: 32729086
DOI: 10.1007/978-1-0716-0787-9_16 -
Zhonghua Kou Qiang Yi Xue Za Zhi =... Jul 2020
Topics: Humans; Odontodysplasia
PubMed: 32634890
DOI: 10.3760/cma.j.cn112144-20190910-00341 -
The British Journal of Dermatology Dec 2020
Topics: Humans; Odontodysplasia
PubMed: 32585735
DOI: 10.1111/bjd.19339 -
Head and Neck Pathology Mar 2021Segmental odontomaxillary dysplasia (SOD) is a developmental condition of the middle and posterior maxilla featuring dysplastic bone overgrowth, dental abnormalities...
Segmental Ipsilateral Odontognathic Dysplasia (Mandibular Involvement in Segmental Odontomaxillary Dysplasia?) and Identification of PIK3CA Somatic Variant in Lesional Mandibular Gingival Tissue.
Segmental odontomaxillary dysplasia (SOD) is a developmental condition of the middle and posterior maxilla featuring dysplastic bone overgrowth, dental abnormalities and, occasionally, various homolateral cutaneous manifestations. Herein, we describe an individual with maxillary abnormality akin to SOD and associated ipsilateral segmental odontomandibular dysplasia. Also, the result of the evaluation of lesional mandibular gingival tissue for overgrowth-related gene variants is reported. An 8-year-old girl presented clinically with congenital maxillary and mandibular alveolar soft tissue enlargement in the area of the premolars. A panoramic radiograph revealed abnormal trabeculation essentially similar to SOD in the maxilla and mandible with congenitally missing maxillary and mandibular first and second premolars and mandibular canines. Diagnostic mandibular bone biopsy was performed and lesional mandibular gingival hyperplastic tissue was obtained for variant analysis of somatic overgrowth genes PIK3CA, AKT1, AKT3, GNAQ, GNA11, MTOR, PIK3R2. Cone beam computerized tomography (CBCT) disclosed osseous abnormalities on the left side of the maxilla and mandible and very mild osseous expansion in the mandible. Histologically, abnormal bone exhibiting prominent reversal lines was present and associated with fibrocollagenous tissue. Genomic DNA analysis disclosed PIK3CAc.1571G>A; pArg524Lys which was seen at a low mosaic level in the blood, indicating a post-zygotic change. Although this case may be a unique disorder, by sharing features with SOD, one can suggest the possibility of mandibular involvement in SOD. The presence of a PIK3CA variant may support the hypothesis that these segmental disorders could be part of the PIK3CA-related overgrowth spectrum.
Topics: Child; Class I Phosphatidylinositol 3-Kinases; Female; Gingival Hyperplasia; Humans; Mandible; Maxilla; Odontodysplasia
PubMed: 32500425
DOI: 10.1007/s12105-020-01185-5 -
American Journal of Medical Genetics.... Jun 2020
Topics: Adolescent; Adult; Aortic Diseases; Dental Enamel Hypoplasia; Female; Heart Diseases; Humans; Interferon-Induced Helicase, IFIH1; Metacarpus; Muscular Diseases; Mutation; Odontodysplasia; Osteoporosis; Vascular Calcification; Young Adult
PubMed: 32202700
DOI: 10.1002/ajmg.a.61556 -
Journal of Dentistry For Children... Jan 2020Segmental odontomaxillary dysplasia (SOD) is a rare craniofacial developmental disorder. Clinical features include abnormal growth and maturation of bone, premolar...
Segmental odontomaxillary dysplasia (SOD) is a rare craniofacial developmental disorder. Clinical features include abnormal growth and maturation of bone, premolar agenesis, delayed eruption of permanent molars, and unilateral posterior maxillary enlargement. Radiographic features include altered bone trabeculae, reduced maxillary sinus, pulp stones, and spontaneous resorption of primary molars. The purpose of this report is to describe the case of a seven-year-old boy who presented with dental pain, erythema of the soft tissues of the right maxillary quadrant, severely infra-occluded primary molars and bony expansion of the maxilla. Surgical exploration under general anesthesia preceded removal of the infraoccluded primary molars and histopathological examination of atypical alveolar bone. The unerupted teeth were examined, mobilized, and left in situ. Following stabilization, a removable prosthesis was constructed to aid esthetics. A comprehensive approach to treatment is indicated in such cases.
Topics: Child; Esthetics, Dental; Follow-Up Studies; Humans; Male; Maxilla; Molar; Odontodysplasia; Tooth, Unerupted
PubMed: 32151309
DOI: No ID Found -
International Journal of Molecular... Oct 2019The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However,...
The dental abnormalities are the typical features of many ectodermal dysplasias along with congenital malformations of nails, skin, hair, and sweat glands. However, several reports of non-syndromic/isolated tooth agenesis have also been found in the literature. The characteristic features of hypohidrotic ectodermal dysplasia (HED) comprise of hypodontia/oligodontia, along with hypohidrosis/anhidrosis, and hypotrichosis. Pathogenic variants in , , , and , cause the phenotypic expression of HED. Genetic alterations in and cause particularly non-syndromic/isolated oligodontia. In the current project, we recruited 57 patients of 17 genetic pedigrees (A-Q) from different geographic regions of the world, including Pakistan, Egypt, Saudi Arabia, and Syria. The molecular investigation of different syndromic and non-syndromic dental conditions, including hypodontia, oligodontia, generalized odontodysplasia, and dental crowding was carried out by using exome and Sanger sequencing. We have identified a novel missense variant (c.311G>A; p.Arg104His) in in three oligodontia patients of family A, two novel sequence variants (c.207delinsTT, p.Gly70Trpfs*25 and c.1300T>G; p.Try434Gly) in in three patients of family B and four patients of family C, respectively. To better understand the structural and functional consequences of missense variants in WNT10A and EDAR on the stability of the proteins, we have performed extensive molecular dynamic (MD) simulations. We have also identified three previously reported pathogenic variants (c.1076T>C; p.Met359Thr), (c.1133C>T; p.Thr378Met) and (c.594_595insC; Gly201Argfs*39) in in family D (four patients), E (two patients) and F (one patient), correspondingly. Presently, our data explain the genetic cause of 18 syndromic and non-syndromic tooth agenesis patients in six autosomal recessive and X-linked pedigrees (A-F), which expand the mutational spectrum of these unique clinical manifestations.
Topics: Ectodermal Dysplasia 1, Anhidrotic; Ectodysplasins; Edar Receptor; Humans; Molecular Dynamics Simulation; Mutation, Missense; Pedigree; Phenotype; Protein Stability; Protein Structure, Tertiary; Exome Sequencing; Wnt Proteins
PubMed: 31652981
DOI: 10.3390/ijms20215282