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World Journal of Pediatrics : WJP Feb 2020Type I interferonopathy is a group of autoinflammatory disorders associated with prominent enhanced type I interferon signaling. The mechanisms are complex, and the... (Review)
Review
BACKGROUNDS
Type I interferonopathy is a group of autoinflammatory disorders associated with prominent enhanced type I interferon signaling. The mechanisms are complex, and the clinical phenotypes are diverse. This review briefly summarized the recent progresses of type I interferonopathy focusing on the clinical and molecular features, pathogeneses, diagnoses and potential therapies.
DATA SOURCES
Original research articles and literature reviews published in PubMed-indexed journals.
RESULTS
Type I interferonopathies include Aicardi-Goutières syndrome, spondyloenchondro-dysplasia with immune dysregulation, stimulator of interferon genes-associated vasculopathy with onset in infancy, X-linked reticulate pigmentary disorder, ubiquitin-specific peptidase 18 deficiency, chronic atypical neutrophilic dermatitis with lipodystrophy, and Singleton-Merten syndrome originally. Other disorders including interferon-stimulated gene 15 deficiency and DNAse II deficiency are believed to be interferonopathies as well. Intracranial calcification, skin vasculopathy, interstitial lung disease, failure to thrive, skeletal development problems and autoimmune features are common. Abnormal responses to nucleic acid stimuli and defective regulation of protein degradation are main mechanisms in disease pathogenesis. First generation Janus kinase inhibitors including baricitinib, tofacitinib and ruxolitinib are useful for disease control. Reverse transcriptase inhibitors seem to be another option for Aicardi-Goutières syndrome.
CONCLUSIONS
Tremendous progress has been made for the discovery of type I interferonopathies and responsible genes. Janus kinase inhibitors and other agents have potential therapeutic roles. Future basic, translational and clinical studies towards disease monitoring and powerful therapies are warranted.
Topics: Aortic Diseases; Autoimmune Diseases; Autoimmune Diseases of the Nervous System; Child; Dental Enamel Hypoplasia; Humans; Immunosuppressive Agents; Interferon Type I; Metacarpus; Muscular Diseases; Nervous System Malformations; Odontodysplasia; Osteoporosis; Phenotype; Protein Kinase Inhibitors; Reverse Transcriptase Inhibitors; Vascular Calcification
PubMed: 31377974
DOI: 10.1007/s12519-019-00273-z -
Journal of Immunology (Baltimore, Md. :... Sep 2019Singleton-Merten syndrome (SMS) is a type I interferonopathy characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, and psoriasis. A...
Singleton-Merten syndrome (SMS) is a type I interferonopathy characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, and psoriasis. A missense mutation in encoding a cytoplasmic viral RNA sensor MDA5 has recently been identified in the SMS patients as well as in patients with a monogenic form of lupus. We previously reported that mice express a constitutively active MDA5 and spontaneously develop lupus-like nephritis. In this study, we demonstrate that the mice also exhibit SMS-like bone abnormalities, including decreased bone mineral density and thin cortical bone. Histological analysis revealed a low number of osteoclasts, low bone formation rate, and abnormal development of growth plate cartilages in mice. These abnormalities were not observed in ・ and ・ mice, indicating the critical role of type I IFNs induced by MDA5/MAVS-dependent signaling in the bone pathogenesis of mice, affecting bone turnover. Taken together, our findings suggest the inhibition of type I IFN signaling as a possible effective therapeutic strategy for bone disorders in SMS patients.
Topics: Animals; Aortic Diseases; Bone Diseases; Bone and Bones; Cartilage; Dental Enamel Hypoplasia; Growth Plate; Interferon-Induced Helicase, IFIH1; Male; Metacarpus; Mice; Mice, Inbred C57BL; Muscular Diseases; Mutation, Missense; Odontodysplasia; Osteoporosis; Vascular Calcification
PubMed: 31366715
DOI: 10.4049/jimmunol.1900354 -
Head and Neck Pathology Mar 2020Regional odontodysplasia (RO) is a rare dental anomaly of unknown etiology that can affect both deciduous and permanent dentition. RO is characterized by severe...
Regional odontodysplasia (RO) is a rare dental anomaly of unknown etiology that can affect both deciduous and permanent dentition. RO is characterized by severe hypoplasia of enamel and dentin, and teeth affected are friable and more susceptible to caries and fractures. Most of the lesions occur in the anterior maxilla and correlation with clinical and radiographic features is essential to provide a correct diagnosis. The major criteria for diagnosis are predominantly based on radiography, which shows presence of large pulp chambers and a marked reduction in the radiopacity of enamel and dentin, making the distinction between these mineralized structures difficult. Early diagnosis is important to minimize future sequels and allow preventive or conservative treatment. The therapeutic approach of the RO should be based on the degree of severity of the anomaly and in the individual functional and aesthetic needs of each case. A classic case of RO affecting the maxilla is exemplified in this Sine Qua Non Radiology-Pathology article.
Topics: Child; Female; Humans; Maxilla; Odontodysplasia
PubMed: 30900210
DOI: 10.1007/s12105-019-01031-3 -
Clinical Oral Investigations Nov 2019Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas oligodontia refers to the absence of...
OBJECTIVE
Tooth agenesis is one of the most common craniofacial developmental anomalies. In hypodontia, one to five teeth are missing, whereas oligodontia refers to the absence of at least six teeth, excluding the third molars. Mutations in several genes including MSX1, PAX9, AXIN2, and WNT10A have been shown to cause non-syndromic tooth agenesis. Regional odontodysplasia (RO), also known as "ghost teeth," is a rare developmental anomaly of tooth formation affecting both dentitions. Some possible causes of RO have been suggested, yet the etiology remains unknown. Because the phenotypes of both oligodontia and RO co-occur in one Finnish family, the aim here was to investigate the genetic etiology of the two conditions.
MATERIALS AND METHODS
A mutation screening of the genes MSX1, PAX9, AXIN2, and WNT10A was performed for the family members of a RO patient and family history of oligodontia.
RESULTS
An initiation codon mutation of the PAX9 gene was found in the proband and segregating with oligodontia in the family.
CONCLUSIONS
The etiology of regional odontodysplasia (RO) may be genetic and the same genes can be involved both in RO and tooth agenesis.
CLINICAL RELEVANCE
Our results give new insights into the etiology of regional odontodysplasia, yet further results are needed.
Topics: Anodontia; Codon, Initiator; Humans; MSX1 Transcription Factor; Mutation; Odontodysplasia; PAX9 Transcription Factor; Pedigree
PubMed: 30809714
DOI: 10.1007/s00784-019-02849-5