title: Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.
abstract: Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.
authors.affiliation: FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.|GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.
authors.forename: Salima
authors.initials: S
authors.lastname: El Chehadeh
authors.affiliation: FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.|GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.|Service de Cytogénétique, CHU de Dijon, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Mosca-Boidron
authors.affiliation: Service de Cytogénétique, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Malan
authors.affiliation: Service de Génétique Clinique, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.affiliation: Service de Génétique Clinique, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Nizon
authors.affiliation: Service de Génétique Clinique Chromosomique et Moléculaire, CHU de Saint-Etienne, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.affiliation: Service de Génétique Clinique Chromosomique et Moléculaire, CHU de Saint-Etienne, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Prieur
authors.affiliation: Service de Génétique Clinique, CLAD Ouest, CHU de Rennes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pasquier
authors.affiliation: GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.|Service de Cytogénétique, CHU de Dijon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Callier
authors.affiliation: FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.|GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lefebvre
authors.affiliation: GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.|Service de Cytogénétique, CHU de Dijon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Marle
authors.affiliation: Service de Génétique Clinique, CLAD Ouest, CHU de Rennes, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Dubourg
authors.affiliation: Service de Génétique Médicale, CHU de Toulouse, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Julia
authors.affiliation: Service de Génétique Médicale, CHU de Clermont-Ferrand, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sarret
authors.affiliation: Service de Génétique Médicale, CHU de Clermont-Ferrand, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Francannet
authors.affiliation: Service de Génétique Médicale, CHU de Clermont-Ferrand, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Laffargue
authors.affiliation: Service de Neuropédiatrie et Maladies Métaboliques, Hôpital Robert Debré, Paris, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Boespflug-Tanguy
authors.affiliation: Service de Génétique Médicale, CHU de Nantes, France.
authors.forename: Albert
authors.initials: A
authors.lastname: David
authors.affiliation: Service de Génétique Médicale, CHU de Nantes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Isidor
authors.affiliation: Service de Génétique Médicale, CHU de Nantes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Le Caignec
authors.affiliation: Service de Génétique Médicale, CHU de Nancy, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Vigneron
authors.affiliation: Service de Génétique Médicale, CHU de Nancy, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Leheup
authors.affiliation: Service de Génétique Médicale, CHU de Nancy, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Lambert
authors.affiliation: Laboratoire de Génétique Médicale, CHU de Nancy, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
authors.affiliation: Service de Neuropédiatrie, CHRU de Lille, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Cuisset
authors.affiliation: Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre, CHRU de Lille, France.
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.affiliation: Service de Génétique, CHU de Caen, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Plessis
authors.affiliation: Service de Génétique, CHRU de Tours, France.
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.affiliation: Service de Génétique Médicale, CHU de Rouen, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Goldenberg
authors.affiliation: Service de Génétique Clinique, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.affiliation: Service de Génétique Clinique, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.affiliation: Laboratoire de Biologie Moléculaire, Hôpital Necker Enfants Malades, Paris, France.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.affiliation: FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.|GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Thevenon
authors.affiliation: Service de Neurologie Pédiatrique, CHU de Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Echenne
authors.affiliation: Service de Génétique, Centre Hospitalier de Vannes, Vannes, France.
authors.forename: Hubert
authors.initials: H
authors.lastname: Journel
authors.affiliation: Service de Génétique, Hôpital Armand Trousseau, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.affiliation: Service de Génétique, Hôpital Armand Trousseau, Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Burglen
authors.affiliation: Laboratoire de Biochimie et Génétique Moléculaire, GH Cochin-Broca-Hôtel Dieu, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
authors.affiliation: Service de Génétique Médicale, CHUV Lausanne, Lausanne, Suisse.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Addor
authors.affiliation: Unité de Neuropédiatrie, CHUV de Lausanne, Lausanne, Suisse.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lebon
authors.affiliation: Laboratoire de Cytogénétique Constitutionnelle et Prénatale, CHUV de Lausanne, Lausanne, Suisse.
authors.forename: Danièle
authors.initials: D
authors.lastname: Martinet
authors.affiliation: Service de Génétique Clinique, Hôpital Robert Debré, Paris, France.
authors.forename: Clarisse
authors.initials: C
authors.lastname: Baumann
authors.affiliation: Service de Génétique Clinique, Hôpital Robert Debré, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Perrin
authors.affiliation: Laboratoire de Biologie Moléculaire, Hôpital Robert Debré, Paris, France.
authors.forename: Séverine
authors.initials: S
authors.lastname: Drunat
authors.affiliation: Département de Génétique et Procréation-UMR CNRS 5525 TIMC-IMAG équipe DYCTIM, CHU Grenoble, France.
authors.forename: Pierre-Simon
authors.initials: PS
authors.lastname: Jouk
authors.affiliation: Département de Génétique et Procréation-UMR CNRS 5525 TIMC-IMAG équipe DYCTIM, CHU Grenoble, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Devillard
authors.affiliation: Département de Génétique et Procréation-UMR CNRS 5525 TIMC-IMAG équipe DYCTIM, CHU Grenoble, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Coutton
authors.affiliation: Service de Génétique Clinique, CHU de Bordeaux, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Lacombe
authors.affiliation: Service de Génétique Clinique, CHU de Bordeaux, France.
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Delrue
authors.affiliation: Département de Génétique Médicale, Hôpital de la Timone, Marseille, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Philip
authors.affiliation: Laboratoire de Génétique Chromosomique, Hôpital de la Timone, Marseille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Moncla
authors.affiliation: Laboratoire de Biologie Moléculaire, Hôpital de la Timone, Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Badens
authors.affiliation: EPICIME-CIC 1407 de Lyon, Inserm, Service de Pharmacologie Clinique, CHU de Lyon, Bron, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Perreton
authors.affiliation: FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel
authors.affiliation: FHU TRANSLAD, Centre de Référence Maladies Rares "Anomalies du Développement et Syndromes Malformatifs" de l'Est, Centre de Génétique, CHU de Dijon, France.|GAD, EA4271, Génétique et Anomalies du Développement, Université de Bourgogne, Dijon, France.
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.affiliation: Service de Neurologie Pédiatrique, CHU de Lyon-GH Est, Bron, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Des Portes
authors.affiliation: Service de Radiologie, Hôpital Femme Mère Enfant, Bron, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Guibaud
mesh_terms: D000293:Adolescent; D000328:Adult; D001927:Brain Diseases / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics* / Q000473:pathology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011379:Prognosis; D055815:Young Adult
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: MECP2 gene; Xq28 duplication; genotype-phenotype correlation; magnetic resonance imaging