title: Clinical and pathologic features of Aicardi-Goutières syndrome due to an IFIH1 mutation: A pediatric case report.
abstract: We describe the case of a young patient with calcifying encephalopathy, born to asymptomatic parents. An extensive hypothesis-driven etiological assessment was performed and failed to detect the precise etiology during many years. We therefore decided to perform whole exome sequencing of the child-unaffected parents trio. A de novo pathogenic variant in the IFIH1 gene which has recently been shown to cause autosomal dominant forms of Aicardi-Goutières syndrome was identified. This child presented with a severe form with neonatal thrombocytopenia and hepatomegaly, the latter having been detected during late gestation. Although first milestones were uneventful, he progressively lost motor skills from the age of 12 months and developed severe spastic paraplegia. Brain imaging revealed white matter abnormalities and extensive calcifications. He also presented atypical skin lesions, different from chilblains. His medical history was marked by two episodes of acute pancreatitis. We provide herein the results of pathological examination including detailed description of the neuropathological hallmarks. To our knowledge, this the first detailed clinico-pathological description of a patient with an IFIH1 pathogenic variant.
authors.affiliation: Pathology Laboratory, Rouen University Hospital, Rouen, France.|ERI28 "NeoVasc", Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Rouen Institute for Biomedical Research, University of Rouen, Rouen, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Marguet
authors.affiliation: Pathology Laboratory, Rouen University Hospital, Rouen, France.|ERI28 "NeoVasc", Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Rouen Institute for Biomedical Research, University of Rouen, Rouen, France.
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Guerrot
authors.affiliation: Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|CNR-MAJ, Rouen University Hospital, Rouen, France.|Inserm U1079, IRIB, Normandie Univ, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Quenez
authors.affiliation: Department of Paediatrics, Rouen University Hospital, Rouen, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Flahaut
authors.affiliation: Department of Paediatrics, Rouen University Hospital, Rouen, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vanhulle
authors.affiliation: Department of Paediatrics, Rouen University Hospital, Rouen, France.
authors.forename: Clémentine
authors.initials: C
authors.lastname: Dumant-Forest
authors.affiliation: Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|Inserm U1079, IRIB, Normandie Univ, Rouen, France.|IRIB Genomics Facility, IRIB, Normandie Univ, Rouen, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Charbonnier
authors.affiliation: Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|Inserm U1079, IRIB, Normandie Univ, Rouen, France.|IRIB Genomics Facility, IRIB, Normandie Univ, Rouen, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Vezain
authors.affiliation: ERI28 "NeoVasc", Laboratory of Microvascular Endothelium and Neonatal Brain Lesions, Rouen Institute for Biomedical Research, University of Rouen, Rouen, France.|Department of Metabolic Biochemistry, Rouen University Hospital, Rouen, France.
authors.forename: Soumeya
authors.initials: S
authors.lastname: Bekri
authors.affiliation: Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|Inserm U1079, IRIB, Normandie Univ, Rouen, France.|IRIB Genomics Facility, IRIB, Normandie Univ, Rouen, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tournier
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|Inserm U1079, IRIB, Normandie Univ, Rouen, France.|IRIB Genomics Facility, IRIB, Normandie Univ, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
authors.affiliation: Department of Genetics, Rouen University Hospital, Rouen, France.|Normandy Centre for Genomic Medicine and Personalized Medicine, Rouen, France.|Inserm U1079, IRIB, Normandie Univ, Rouen, France.|IRIB Genomics Facility, IRIB, Normandie Univ, Rouen, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Nicolas
mesh_terms: D000293:Adolescent; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D001927:Brain Diseases / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D000072640:Interferon-Induced Helicase, IFIH1 / Q000235:genetics*; D008297:Male; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D010264:Paraplegia / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology
chemical_list: C452815:IFIH1 protein, human; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Aicardi-Goutières syndrome; IFIH1; calcification; calcifying encephalopathy; exome; neuropathology; trio; type I-interferonopathies