title: MECP2 gene mutation analysis in the British and Italian Rett Syndrome patients: hot spot map of the most recurrent mutations and bioinformatic analysis of a new MECP2 conserved region.
abstract: Rett syndrome (RTT) is an X-linked dominant neurological disorder, which appears to be the most common genetic cause of profound combined intellectual and physical disability in Caucasian females. This syndrome has been associated with mutations of the MECP2 gene, a transcriptional repressor of unknown target genes. We report a detailed mutational analysis of a large cohort of RTT patients from the UK and Italy. This study has permitted us to produce a hot spot map of the mutations identified. Bioinformatic analysis of the mutations, taking advantage of structural and evolutionary data, leads us to postulate the existence of a new functional domain in the MeCP2 protein, conserved among brain-specific regulatory factors.
authors.affiliation: International Institute of Genetics and Biophysics, CNR, Via Marconi 10, 80125, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vacca
authors.forename: F
authors.initials: F
authors.lastname: Filippini
authors.forename: A
authors.initials: A
authors.lastname: Budillon
authors.forename: V
authors.initials: V
authors.lastname: Rossi
authors.forename: F
authors.initials: F
authors.lastname: Della Ragione
authors.forename: M L
authors.initials: ML
authors.lastname: De Bonis
authors.forename: G
authors.initials: G
authors.lastname: Mercadante
authors.forename: E
authors.initials: E
authors.lastname: Manzati
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.forename: S
authors.initials: S
authors.lastname: Bigoni
authors.forename: C
authors.initials: C
authors.lastname: Trabanelli
authors.forename: G
authors.initials: G
authors.lastname: Pini
authors.forename: E
authors.initials: E
authors.lastname: Calzolari
authors.forename: A
authors.initials: A
authors.lastname: Ferlini
authors.forename: I
authors.initials: I
authors.lastname: Meloni
authors.forename: G
authors.initials: G
authors.lastname: Hayek
authors.forename: M
authors.initials: M
authors.lastname: Zappella
authors.forename: A
authors.initials: A
authors.lastname: Renieri
authors.forename: M
authors.initials: M
authors.lastname: D'Urso
authors.forename: M
authors.initials: M
authors.lastname: D'Esposito
authors.forename: F
authors.initials: F
authors.lastname: Macdonald
authors.forename: A
authors.initials: A
authors.lastname: Kerr
authors.forename: S
authors.initials: S
authors.lastname: Dhanjal
authors.forename: M
authors.initials: M
authors.lastname: Hulten
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone; D002874:Chromosome Mapping; D019295:Computational Biology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007558:Italy; D051783:Methyl-CpG-Binding Protein 2; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D006113:United Kingdom
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009687:Nuclear Proteins; D012097:Repressor Proteins; D014157:Transcription Factors