title: Comprehensive diagnosis of Rett's syndrome relying on genetic, epigenetic and expression evidence of deficiency of the methyl-CpG-binding protein 2 gene: study of a cohort of Israeli patients.
abstract: BACKGROUND
  Despite advances in the characterisation of mutations in the MECP2-coding region, a small proportion of classic RTT cases remain without recognisable mutations.
  
  
  OBJECTIVE
  To identify previously unknown mutations, a quantitative assay was established, providing estimates of MECP2_e1 and MECP2_e2 expression levels in peripheral blood. A systematic analysis of an Israeli cohort of 82 patients with classic and atypical RTT is presented, including sequence analysis of the MECP2-coding region, MLPA, XCI and quantitative expression assays.
  
  
  CONCLUSIONS
  A novel mis-sense mutation at ca 453C-->T (pD151E), resulting in a change of a conserved residue at the methyl-binding domain, and a rare GT deletion of intron 1 donor splice site are reported. It is shown that various MECP2 mutations had distinct effects on MECP2 expression levels in peripheral blood. The most significant (p<0.001) reduction in the expression of both MECP2 isoforms was related to the presence of the intron 1 donor splice-site mutation. Using quantitative expression assays, it was shown that several patients with classic and atypical RTT with no mutation findings had significantly lower MECP2 expression levels. Further research on these patients may disclose still elusive non-coding regulatory MECP2 mutations.
authors.forename: Y
authors.initials: Y
authors.lastname: Petel-Galil
authors.forename: B
authors.initials: B
authors.lastname: Benteer
authors.forename: Y P
authors.initials: YP
authors.lastname: Galil
authors.forename: B B
authors.initials: BB
authors.lastname: Zeev
authors.forename: I
authors.initials: I
authors.lastname: Greenbaum
authors.forename: M
authors.initials: M
authors.lastname: Vecsler
authors.forename: B
authors.initials: B
authors.lastname: Goldman
authors.forename: H
authors.initials: H
authors.lastname: Lohi
authors.forename: B A
authors.initials: BA
authors.lastname: Minassian
authors.forename: E
authors.initials: E
authors.lastname: Gak
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007557:Israel; D051783:Methyl-CpG-Binding Protein 2 / Q000097:blood / Q000172:deficiency / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D015203:Reproducibility of Results; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2