Further evidence for specific IFIH1 mutation as a cause of Singleton-Merten syndrome with phenotypic heterogeneity.
Singleton-Merten syndrome (MIM 182250) is an autosomal dominant inherited disorder characterized by early onset periodontitis, root resorption, osteopenia, osteoporosis, and aortic valve or thoracic aorta calcification. The disorder can have significant intrafamilial phenotypic variability. Here, we present a mother and daughter with Singleton-Merten syndrome harboring a previously described pathogenic missense mutation, c.2465G>A p.(Arg822Gln), in IFIH1 (interferon induced with helicase C domain 1), encoding MDA5 (Melanoma Differentiation-Associated protein 5). These data confirm the pathogenicity of IFIH1 c.2465G>A p.(Arg822Gln) for Singleton-Merten syndrome and affirm the striking phenotypic heterogeneity of this disorder. In addition, we expand the Singleton-Merten phenotype by adding severe systemic lupus erythematosus (SLE) to the clinical picture. Investigations of known SLE genes as well as a single nucleotide polymorphism suggested to be involved in development of SLE were normal.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Maria
http://orcid.org/0000-0003-3120-1625
M
Pettersson
National Oral Disability Centre for Rare Disorders, The Institute for Postgraduate Dental Education, Jönköping, Sweden.|School of Health and Welfare, Jönköping University, Jönköping, Sweden.
Birgitta
B
Bergendal
National Oral Disability Centre for Rare Disorders, The Institute for Postgraduate Dental Education, Jönköping, Sweden.|School of Health and Welfare, Jönköping University, Jönköping, Sweden.
Johanna
J
Norderyd
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.|Science for Life Laboratory, Karolinska Institutet Science Park, Solna, Sweden.
Daniel
D
Nilsson
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Britt-Marie
BM
Anderlid
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Ann
A
Nordgren
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.|Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
Anna
A
Lindstrand
D000328:Adult; D001018:Aortic Diseases / Q000235:genetics* / Q000503:physiopathology; D003744:Dental Enamel Hypoplasia / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000503:physiopathology; D008663:Metacarpus / Q000002:abnormalities* / Q000503:physiopathology; D009135:Muscular Diseases / Q000235:genetics* / Q000503:physiopathology; D020125:Mutation, Missense; D018126:Odontodysplasia / Q000235:genetics* / Q000503:physiopathology; D010024:Osteoporosis / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D061205:Vascular Calcification / Q000235:genetics* / Q000503:physiopathology
C452815:IFIH1 protein, human; D000072640:Interferon-Induced Helicase, IFIH1
IFIH1; Singleton-Merten syndrome; exome sequencing