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Contemporary Clinical Dentistry 2015Regional odontodysplasia (RO) is a rare developmental anomaly involving both mesodermal and ectodermal components in primary or permanent dentition. It affects the...
Regional odontodysplasia (RO) is a rare developmental anomaly involving both mesodermal and ectodermal components in primary or permanent dentition. It affects the maxilla and the mandible or both; however, maxilla is more commonly involved. This article reports the case of 33-month-old boy who came with the chief complaint of delayed eruption of mandibular teeth. Findings of clinical and radiographic examination were consistent with those of RO. Maxillary dentition was unaffected. Clinical and radiographic features and treatment options are discussed.
PubMed: 26097362
DOI: 10.4103/0976-237X.156054 -
American Journal of Human Genetics Feb 2015Singleton-Merten syndrome (SMS) is an infrequently described autosomal-dominant disorder characterized by early and extreme aortic and valvular calcification, dental...
Singleton-Merten syndrome (SMS) is an infrequently described autosomal-dominant disorder characterized by early and extreme aortic and valvular calcification, dental anomalies (early-onset periodontitis and root resorption), osteopenia, and acro-osteolysis. To determine the molecular etiology of this disease, we performed whole-exome sequencing and targeted Sanger sequencing. We identified a common missense mutation, c.2465G>A (p.Arg822Gln), in interferon induced with helicase C domain 1 (IFIH1, encoding melanoma differentiation-associated protein 5 [MDA5]) in four SMS subjects from two families and a simplex case. IFIH1 has been linked to a number of autoimmune disorders, including Aicardi-Goutières syndrome. Immunohistochemistry demonstrated the localization of MDA5 in all affected target tissues. In vitro functional analysis revealed that the IFIH1 c.2465G>A mutation enhanced MDA5 function in interferon beta induction. Interferon signature genes were upregulated in SMS individuals' blood and dental cells. Our data identify a gain-of-function IFIH1 mutation as causing SMS and leading to early arterial calcification and dental inflammation and resorption.
Topics: Amino Acid Sequence; Aortic Diseases; Arteries; Base Sequence; Calcinosis; DEAD-box RNA Helicases; Dental Enamel Hypoplasia; Exome; Genes, Dominant; Humans; Immunohistochemistry; Interferon-Induced Helicase, IFIH1; Interferon-beta; Metacarpus; Models, Molecular; Molecular Sequence Data; Muscular Diseases; Mutation, Missense; Odontodysplasia; Osteoporosis; Pedigree; Phenotype; Sequence Analysis, DNA; Tooth Abnormalities; Vascular Calcification
PubMed: 25620204
DOI: 10.1016/j.ajhg.2014.12.014 -
American Journal of Human Genetics Feb 2015Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma,...
Singleton-Merten syndrome (SMS) is an autosomal-dominant multi-system disorder characterized by dental dysplasia, aortic calcification, skeletal abnormalities, glaucoma, psoriasis, and other conditions. Despite an apparent autosomal-dominant pattern of inheritance, the genetic background of SMS and information about its phenotypic heterogeneity remain unknown. Recently, we found a family affected by glaucoma, aortic calcification, and skeletal abnormalities. Unlike subjects with classic SMS, affected individuals showed normal dentition, suggesting atypical SMS. To identify genetic causes of the disease, we performed exome sequencing in this family and identified a variant (c.1118A>C [p.Glu373Ala]) of DDX58, whose protein product is also known as RIG-I. Further analysis of DDX58 in 100 individuals with congenital glaucoma identified another variant (c.803G>T [p.Cys268Phe]) in a family who harbored neither dental anomalies nor aortic calcification but who suffered from glaucoma and skeletal abnormalities. Cys268 and Glu373 residues of DDX58 belong to ATP-binding motifs I and II, respectively, and these residues are predicted to be located closer to the ADP and RNA molecules than other nonpathogenic missense variants by protein structure analysis. Functional assays revealed that DDX58 alterations confer constitutive activation and thus lead to increased interferon (IFN) activity and IFN-stimulated gene expression. In addition, when we transduced primary human trabecular meshwork cells with c.803G>T (p.Cys268Phe) and c.1118A>C (p.Glu373Ala) mutants, cytopathic effects and a significant decrease in cell number were observed. Taken together, our results demonstrate that DDX58 mutations cause atypical SMS manifesting with variable expression of glaucoma, aortic calcification, and skeletal abnormalities without dental anomalies.
Topics: Adult; Aortic Diseases; Base Sequence; Cells, Cultured; Child, Preschool; DEAD Box Protein 58; DEAD-box RNA Helicases; Dental Enamel Hypoplasia; Exome; Female; Genes, Dominant; Glaucoma; Humans; Male; Metacarpus; Models, Molecular; Molecular Sequence Data; Muscular Diseases; Musculoskeletal Abnormalities; Mutation, Missense; Odontodysplasia; Osteoporosis; Pedigree; Polymorphism, Single Nucleotide; Radiography; Receptors, Immunologic; Sequence Analysis, DNA; Vascular Calcification
PubMed: 25620203
DOI: 10.1016/j.ajhg.2014.11.019 -
BMJ Case Reports Sep 2014Singleton Merten Syndrome is an autosomal dominant disorder of unknown origin. Patients often present with muscular weakness, failure to thrive, abnormal dentition,...
Singleton Merten Syndrome is an autosomal dominant disorder of unknown origin. Patients often present with muscular weakness, failure to thrive, abnormal dentition, glaucoma, psoriatic skin lesions, aortic calcification and musculoskeletal abnormalities. In this case, we present a young girl with a history of aortic root replacement, who had an unusual progressive supra-aortic stenosis managed with urgent surgery during the course of the syndrome. Cardiovascular involvement needs special attention, since it is the major cause of mortality along with rhythm disturbances in the course of Singleton Merten Syndrome.
Topics: Aortic Diseases; Aortic Valve Stenosis; Brain; Calcinosis; Child; Dental Enamel Hypoplasia; Disease Progression; Female; Humans; Metacarpus; Muscular Diseases; Odontodysplasia; Osteoporosis; Radiography; Recurrence; Syncope; Vascular Calcification
PubMed: 25193816
DOI: 10.1136/bcr-2014-205985