title: Mosaic Tetrasomy 9p: A Mendelian Condition Associated With Pediatric-Onset Overlap Myositis.
abstract: Pediatric-onset inflammatory myositis (IM) and systemic lupus erythematosus (SLE) are rare inflammatory diseases. Both result from the complex interaction of genetic and environmental factors. An increasing number of Mendelian conditions predisposing to the development of SLE have been recently identified. These include monogenic conditions, referred to as the type I interferonopathies, associated with a primary upregulation of type I interferon (IFN), a key cytokine in the pathogenesis of SLE and some cases of IM. Here, we report on a pediatric-onset inflammatory overlap phenotype in a 6-year-old girl who was shown to carry mosaic tetrasomy 9p. The patient presented with myositis overlapping with lupuslike features. Myositis was characterized by a proximal muscular weakness and HLA class I antigen myofiber overexpression on muscle biopsy. Lupus-like manifestations consisted of pericarditis, pleuritis, and positive antinuclear and anti-SSA (Sjögren-syndrome A) antibodies. Complete remission was achieved with corticosteroids and mycophenolate mofetyl. Analysis of tetrasomy 9p showed mosaic tetrasomy in the 9p24.3q12 region, including the type I IFN cluster, and increased expression of IFN-stimulated genes. These data suggest that mosaic tetrasomy 9p can be associated with an upregulation of type I IFN signaling, predisposing to inflammatory myositis and lupus-like features. Thus, unexplained muscle or other organ involvement in patients carrying mosaic tetrasomy of the type IFN cluster of chromosome 9p should lead to the search for IM and/or lupuslike disease, and karyotype should be performed in patients with SLE or IM with mental retardation.
authors.affiliation: Service de Pédiatrie, Université Paris 13, Sorbonne Paris Cité, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris (AP-HP), Bondy Cedex, France; Unité d'Immunologie, Hématologie et Rhumatologie Pédiatriques; marie-louise.fremond@jvr.aphp.fr.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Frémond
authors.affiliation: Service de Neurologie Pédiatrique, Centre de Référence des Maladies Neuromusculaires, Hôpital Necker Enfants Malades, AP-HP, Paris, France;
authors.forename: Cyril
authors.initials: C
authors.lastname: Gitiaux
authors.affiliation: M3C-Necker, Congenital and Pediatric Cardiology, Hôpital Necker-Enfants Malades, AP-HP, Paris, France;
authors.forename: Damien
authors.initials: D
authors.lastname: Bonnet
authors.affiliation: Service de Pédiatrie, Université Paris 13, Sorbonne Paris Cité, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris (AP-HP), Bondy Cedex, France;
authors.forename: Tamazoust
authors.initials: T
authors.lastname: Guiddir
authors.affiliation: Manchester Centre for Genomic Medicine, Institute of Human Development Faculty of Medical and Human Sciences, Manchester Academic Health Sciences Centre, University of Manchester, Manchester, United Kingdom; and Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
authors.affiliation: Service de Pédiatrie, Université Paris 13, Sorbonne Paris Cité, Hôpital Jean Verdier, Assistance Publique-Hôpitaux de Paris (AP-HP), Bondy Cedex, France;
authors.forename: Loïc
authors.initials: L
authors.lastname: de Pontual
authors.affiliation: Unité d'Immunologie, Hématologie et Rhumatologie Pédiatriques; Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Laboratory of Neurogenetics and Neuroinflammation, Paris, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
mesh_terms: D000782:Aneuploidy; D002648:Child; D002899:Chromosomes, Human, Pair 9; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics*; D009030:Mosaicism; D009220:Myositis / Q000150:complications / Q000235:genetics*