Dataset Information

MDA5-Associated Neuroinflammation and the Singleton-Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum.

ABSTRACT: In 1973, Singleton and Merten described a new syndrome in 2 female probands with aortic and cardiac valve calcifications, early loss of secondary dentition, and widened medullary cavities of the phalanges. In 1984, Aicardi and Goutières defined a phenotype resembling congenital viral infection with basal ganglia calcification and increased protein content in the cerebrospinal fluid. Between 2006 and 2012, mutations in 6 different genes were described to be associated with Aicardi-Goutières syndrome, specifically-TREX1, RNASEH2A, RNASEH2B, RNASEH2C, ADAR, and SAMHD1. More recently, mutations in IFIH1 were reported in a variety of neuroimmunological phenotypes, including Aicardi-Goutières syndrome, while a specific Arg822Gln mutation in IFIH1 was described in 3 discrete families with Singleton-Merten syndrome (SMS). IFIH1 encodes for melanoma differentiation-associated gene 5 (MDA5), and all mutations identified to date have been associated with an enhanced interferon response in affected individuals. In this study, we present a male child demonstrating recurrent febrile episodes, spasticity, and basal ganglia calcification suggestive of Aicardi-Goutières syndrome, who carries the same Arg822Gln mutation in IFIH1 previously associated with SMS. We conclude that both diseases are part of the interferonopathy grouping and that the Arg822Gln mutation in IFIH1 can cause a spectrum of disease, including neurological involvement.

SUBMITTER: Buers I

PROVIDER: S-EPMC5439407 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

MDA5-Associated Neuroinflammation and the Singleton-Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum.

Buers Insa I Rice Gillian I GI Crow Yanick J YJ Rutsch Frank F

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 20170501 5

In 1973, Singleton and Merten described a new syndrome in 2 female probands with aortic and cardiac valve calcifications, early loss of secondary dentition, and widened medullary cavities of the phalanges. In 1984, Aicardi and Goutières defined a phenotype resembling congenital viral infection with basal ganglia calcification and increased protein content in the cerebrospinal fluid. Between 2006 and 2012, mutations in 6 different genes were described to be associated with Aicardi-Goutières syndr ...[more]

PMID: 28475458

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Project description:Non coding RNAs (ncRNAs) have emerged as regulators of human carcinogenesis by affecting the expression of key tumor suppressor genes and oncogenes. They are divided into short and long ncRNAs, according to their length. Circular RNAs (circRNAs) are included in the second group and were recently discovered as being originated by back-splicing, joining either single or multiple exons, or exons with retained introns. The human Plasmacytoma Variant Translocation 1 (PVT1) gene maps on the long arm of chromosome 8 (8q24) and encodes for 52 ncRNAs variants, including 26 linear and 26 circular isoforms, and 6 microRNAs. PVT1 genomic locus is 54 Kb downstream to MYC and several interactions have been described among these two genes, including a feedback regulatory mechanism. MYC-independent functions of PVT1/circPVT1 have been also reported, especially in the regulation of immune responses. We here review and discuss the role of both PVT1 and circPVT1 in the hematopoietic system. No information is currently available concerning their transforming ability in hematopoietic cells. However, present literature supports their cooperation with a more aggressive and/or undifferentiated cell phenotype, thus contributing to cancer progression. PVT1/circPVT1 upregulation through genomic amplification or rearrangements and/or increased transcription, provides a proliferative advantage to malignant cells in acute myeloid leukemia, acute promyelocytic leukemia, Burkitt lymphoma, multiple myeloma (linear PVT1) and acute lymphoblastic leukemia (circPVT1). In addition, PVT1 and circPVT1 regulate immune responses: the overexpression of the linear form in myeloid derived suppressor cells induced immune tolerance in preclinical tumor models and circPVT1 showed immunosuppressive properties in myeloid and lymphoid cell subsets. Overall, these recent data on PVT1 and circPVT1 functions in hematological malignancies and immune responses reflect two faces of the same coin: involvement in cancer progression by promoting a more aggressive phenotype of malignant cells and negative regulation of the immune system as a novel potential therapy-resistance mechanism.

Dataset Information

MDA5-Associated Neuroinflammation and the Singleton-Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum.

Publications

MDA5-Associated Neuroinflammation and the Singleton-Merten Syndrome: Two Faces of the Same Type I Interferonopathy Spectrum.

Similar Datasets

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