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

被引:21
作者
Buers, Insa [1 ]
Rice, Gillian I. [2 ]
Crow, Yanick J. [2 ,3 ,4 ]
Rutsch, Frank [1 ]
机构
[1] Muenster Univ, Childrens Hosp, Dept Gen Pediat, Albert Schweitzer Campus 1, D-48149 Munster, Germany
[2] Univ Manchester, Sch Biol Sci, Fac Biol Med & Hlth, Div Evolut & Genom Sci, Manchester, Lancs, England
[3] INSERM, UMR 1163, Lab Neurogenet & Neuroinflammat, Paris, France
[4] Paris Descartes Sorbonne Paris Cite Univ, Inst Imagine, Paris, France
基金
欧洲研究理事会;
关键词
Singleton-Merten syndrome; Aicardi-Goutieres syndrome; IFIH1; AICARDI-GOUTIERES-SYNDROME; OF-FUNCTION MUTATION; RIG-I; DSRNA RECOGNITION; MDA5; FILAMENTS; GAIN; RNA; ACTIVATION; HELICASE; DISEASE;
D O I
10.1089/jir.2017.0004
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 Goutieres 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-Goutieres syndrome, specifically-TREX1, RNASEH2A, RNA-SEH2B, RNASEH2C, ADAR, and SAMHD1. More recently, mutations in IFIH1 were reported in a variety of neuroimmunological phenotypes, including Aicardi-Goutieres 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-Goutieres 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.
引用
收藏
页码:214 / 219
页数:6
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