title: Asperger syndrome and early-onset schizophrenia associated with a novel MECP2 deleterious missense variant.
abstract: Methyl-CpG-binding protein 2 (MECP2) deleterious variants, which are responsible for Rett syndrome in girls, are involved in a wide spectrum of developmental disabilities in males. A neuropsychiatric phenotype without intellectual disability is uncommon in patients with MECP2 deleterious variants. We report on two dizygotic twins with an MECP2-related psychiatric disorder without intellectual disability. Neuropsychological and psychiatric phenotype assessments were performed, and a genetic analysis was carried out. Both patients fulfilled the Pervasive Developmental Disorder criteria on Autism Diagnostic Observation Schedule and Asperger syndrome criteria on Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV). One patient developed early-onset schizophrenia (DSM-IV criteria) with two acute psychotic episodes, the latest one following corticosteroids and sodium valproate intake, with major hyperammonemia. A novel MECP2 gene transversion c.491 G>T [p.(Ser164Ile)] was found in both twins. Pathogenicity of this variant was considered on the basis of strong clinical and molecular data. The underlying molecular basis of neuropsychiatric disorders may have important consequences on genetic counseling and therapeutic strategies.
authors.affiliation: aClaude Bernard Lyon 1 University bInstitute of Cognitive Science, CNRS UMR 5304 cFrench National Reference Center for Rare Diseases with Intellectual Disability dReference Center on Learning Disabilities, Pediatric Functional Rehabilitation Department, Escale, Women Mothers and Children Hospital eDepartment of Child Psychiatry, Neurological Hospital fDepartment of Medical Genetics, Lyon University Hospital gCNRS UMR 5292, INSERM U1028, CNRL hDepartment of Child Psychiatry, Saint Jean de Dieu Hospital, Lyon, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Curie
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Lesca
authors.forename: Gérald
authors.initials: G
authors.lastname: Bussy
authors.forename: Sabine
authors.initials: S
authors.lastname: Manificat
authors.forename: Valérie
authors.initials: V
authors.lastname: Arnaud
authors.forename: Sibylle
authors.initials: S
authors.lastname: Gonzalez
authors.forename: Olivier
authors.initials: O
authors.lastname: Revol
authors.forename: Alain
authors.initials: A
authors.lastname: Calender
authors.forename: Daniel
authors.initials: D
authors.lastname: Gérard
authors.forename: Vincent
authors.initials: V
authors.lastname: des Portes
mesh_terms: D020817:Asperger Syndrome / Q000235:genetics* / Q000378:metabolism; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020125:Mutation, Missense / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D012561:Schizophrenia, Childhood / Q000235:genetics*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2