title: Cytogenetic and molecular characterization of a recombinant X chromosome in a family with a severe neurologic phenotype and macular degeneration.
abstract: BACKGROUND
  Duplications of MECP2 gene in males cause a syndrome characterized by distinctive clinical features, including severe to profound mental retardation, infantile hypotonia, mild dysmorphic features, poor speech development, autistic features, seizures, progressive spasticity and recurrent infections. Patients with complex chromosome rearrangements, leading to Xq28 duplication, share most of the clinical features of individuals with tandem duplications, in particular neurologic problems, suggesting a major pathogenetic role of MECP2 overexpression.
  
  
  RESULTS
  We performed cytogenetic and molecular cytogenetic studies in a previously described family with affected males showing congenital ataxia, late-onset progressive myoclonic encephalopathy and selective macular degeneration. Microsatellite, FISH and array-CGH analyses identified a recombinant X chromosome with a deletion of the PAR1 region, encompassing SHOX, replaced by a duplicated segment of the Xq28 terminal portion, including MECP2.
  
  
  CONCLUSIONS
  Our report describes the identification of the actual genetic cause underlying a severe syndrome that previous preliminary analyses erroneously associated to a terminal Xp22.33 region. In the present family as well as in previously reported patients with similar rearrangements, the observed neurologic phenotype is ascribable to MECP2 duplication, with an undefined contribution of the other involved genes. Maculopathy, presented by affected males reported here, could be a novel clinical feature associated to Xq28 disomy due to recombinant X chromosomes, but at present the underlying pathogenetic mechanism is unknown and this potential clinical correlation should be confirmed through the collection of additional patients.
authors.affiliation: U.O. Genetica Medica, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, via Massarenti, 9, Bologna, 40138 Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Magini
authors.affiliation: S.S.V.D. Biologia Molecolare, Citogenetica, Citomorfologia Ematica e Vaginale, Ospedale Belcolle, Viterbo, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Poscente
authors.affiliation: U.O. Genetica Medica, AOU di Bologna, Policlinico S. Orsola-Malpighi, Bologna, 40138 Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Centro Interdipartimentale per la Ricerca Industriale Scienze della Vita e Tecnologie per la Salute, Università di Bologna, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Vargiolu
authors.affiliation: Dipartimento di Farmacia e Biotecnologie, Università di Bologna, Bologna, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bacchelli
authors.affiliation: U.O. Genetica Medica, AOU di Bologna, Policlinico S. Orsola-Malpighi, Bologna, 40138 Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Graziano
authors.affiliation: U.O. Genetica Medica, AOU di Bologna, Policlinico S. Orsola-Malpighi, Bologna, 40138 Italy.|S.S.D. Genetica Clinica, Arcispedale S. Maria Nuova-Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
authors.forename: Anita
authors.initials: A
authors.lastname: Wischmeijer
authors.affiliation: U.O. Genetica Medica, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, via Massarenti, 9, Bologna, 40138 Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Turchetti
authors.affiliation: U.O. Neuropsichiatria Infantile, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, Bologna, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Malaspina
authors.affiliation: U.O. Neuropsichiatria Infantile, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, Bologna, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Marchiani
authors.affiliation: U.O. Neuropsichiatria Infantile, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, Bologna, Italy.
authors.forename: Duccio Maria
authors.initials: DM
authors.lastname: Cordelli
authors.affiliation: U.O. Neuropsichiatria Infantile, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, Bologna, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Franzoni
authors.affiliation: U.O. Genetica Medica, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, via Massarenti, 9, Bologna, 40138 Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Romeo
authors.affiliation: U.O. Genetica Medica, Policlinico Sant'Orsola-Malpighi, DIMEC, Università di Bologna, via Massarenti, 9, Bologna, 40138 Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
keywords: MECP2 duplication; Macular degeneration; Recombinant X chromosome; Xq28 disomy