title: Rett syndrome in Spain: mutation analysis and clinical correlations.
abstract: Rett syndrome (RTT) is an X-linked neurodevelopmental disease that affects girls almost exclusively. In a high proportion of patients the disease is caused by de novo mutations at the MECP2 gene, encoding methyl-CpG-binding protein 2. With the aim to characterize the spectrum of mutations in a series of sporadic RTT patients, including an affected male, and to relate the genetic results to the clinical features of the disease, a clinical checklist and a score system were elaborated to evaluate the clinical severity of the disease. Mutation analysis of the MECP2 coding region was done by direct sequencing. De novo mutations were found in 60% of the patients, including both classic and atypical forms. The change R133H was identified in a 13-year-old boy showing a classic RTT phenotype and normal karyotype. Significant differences were observed among missense and truncating mutations regarding disease severity, age of onset of stereotypies, and the ability of the patients to sit alone and to walk.
authors.affiliation: Genetics Section, Hospital Sant Joan de Déu, Av. Sant Joan de Déu 2, 08950 Esplugues, Barcelona, Spain. emonros@hjsdbcn.org
authors.forename: E
authors.initials: E
authors.lastname: Monrós
authors.forename: J
authors.initials: J
authors.lastname: Armstrong
authors.forename: E
authors.initials: E
authors.lastname: Aibar
authors.forename: P
authors.initials: P
authors.lastname: Poo
authors.forename: I
authors.initials: I
authors.lastname: Canós
authors.forename: M
authors.initials: M
authors.lastname: Pineda
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020233:Gait Disorders, Neurologic / Q000235:genetics / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051783:Methyl-CpG-Binding Protein 2; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D010641:Phenotype; D017434:Protein Structure, Tertiary / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D015518:Rett Syndrome / Q000235:genetics* / Q000503:physiopathology*; D012737:Sex Factors; D013030:Spain; D013064:Speech Disorders / Q000235:genetics / Q000503:physiopathology; D019956:Stereotypic Movement Disorder / Q000235:genetics / Q000503:physiopathology
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins