title: Recent insights into genotype-phenotype relationships in patients with Rett syndrome using a fine grain scale.
abstract: Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder affecting around 1 in 10,000 female births. The clinical picture of RTT appears quite heterogeneous for each single feature. Mutations in MECP2 gene have been associated with the onset of RTT. The most known gene function consists of transcriptional repression of specific target genes, mainly by the binding of its methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co-repressors and histone deacetylase binding to DNA by its transcription repressor domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT) patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype-phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as producing mild impairment, was associated to a moderate phenotype in which behavioural characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference concerned prevalently the motor-functional and autonomy skills of the patients, affecting the management of everyday activities.
authors.affiliation: Department of Cognitive Science, Education and Cultural Studies, University of Messina, via Concezione 8, 98122 Messina, Italy. Electronic address: rafabio@unime.it.
authors.forename: Rosa Angela
authors.initials: RA
authors.lastname: Fabio
authors.affiliation: Department of Psychology, Catholic University of the Sacred Heart, Largo Gemelli 1, 20123 Milano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Colombo
authors.affiliation: Cytogenetics and Molecular Genetics Laboratory, Istituto Auxologico Italiano, via Ariosto 13, 20145 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
authors.affiliation: Cytogenetics and Molecular Genetics Laboratory, Istituto Auxologico Italiano, via Ariosto 13, 20145 Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cogliati
authors.affiliation: Cytogenetics and Molecular Genetics Laboratory, Istituto Auxologico Italiano, via Ariosto 13, 20145 Milano, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Masciadri
authors.affiliation: Department of Psychology, Catholic University of the Sacred Heart, Largo Gemelli 1, 20123 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Foglia
authors.affiliation: Department of Psychology, Catholic University of the Sacred Heart, Largo Gemelli 1, 20123 Milano, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonietti
authors.affiliation: Department of Psychology, Catholic University of the Sacred Heart, Largo Gemelli 1, 20123 Milano, Italy; Laboratory of Cellular Biochemistry and Molecular Biology-CRIBENS, Catholic University of the Sacred Heart, Piazza Buonarroti 30, 20145 Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tavian
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D015518:Rett Syndrome / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D055815:Young Adult
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: Autonomy; Cognitive processes; Emotion; MECP2; Motor behaviour; Rett syndrome