title: Gross rearrangements of the MECP2 gene are found in both classical and atypical Rett syndrome patients.
abstract: MECP2 mutations are identifiable in approximately 80% of classic Rett syndrome (RTT), but less frequently in atypical RTT. We recruited 110 patients who fulfilled the diagnostic criteria for Rett syndrome and were referred to Cardiff for molecular analysis, but in whom an MECP2 mutation was not identifiable. Dosage analysis of MECP2 was carried out using multiplex ligation dependent probe amplification or quantitative fluorescent PCR. Large deletions were identified in 37.8% (14/37) of classic and 7.5% (4/53) of atypical RTT patients. Most large deletions contained a breakpoint in the deletion prone region of exon 4. The clinical phenotype was ascertained in all 18 of the deleted cases and in four further cases with large deletions identified in Goettingen. Five patients with large deletions had additional congenital anomalies, which was significantly more than in RTT patients with other MECP2 mutations (2/193; p<0.0001). Quantitative analysis should be included in molecular diagnostic strategies in both classic and atypical RTT.
authors.forename: H L
authors.initials: HL
authors.lastname: Archer
authors.forename: S D
authors.initials: SD
authors.lastname: Whatley
authors.forename: J C
authors.initials: JC
authors.lastname: Evans
authors.forename: D
authors.initials: D
authors.lastname: Ravine
authors.forename: P
authors.initials: P
authors.lastname: Huppke
authors.forename: A
authors.initials: A
authors.lastname: Kerr
authors.forename: D
authors.initials: D
authors.lastname: Bunyan
authors.forename: B
authors.initials: B
authors.lastname: Kerr
authors.forename: E
authors.initials: E
authors.lastname: Sweeney
authors.forename: S J
authors.initials: SJ
authors.lastname: Davies
authors.forename: W
authors.initials: W
authors.lastname: Reardon
authors.forename: J
authors.initials: J
authors.lastname: Horn
authors.forename: K D
authors.initials: KD
authors.lastname: MacDermot
authors.forename: R A
authors.initials: RA
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Magee
authors.forename: A
authors.initials: A
authors.lastname: Donaldson
authors.forename: Y
authors.initials: Y
authors.lastname: Crow
authors.forename: G
authors.initials: G
authors.lastname: Hermon
authors.forename: Z
authors.initials: Z
authors.lastname: Miedzybrodzka
authors.forename: D N
authors.initials: DN
authors.lastname: Cooper
authors.forename: L
authors.initials: L
authors.lastname: Lazarou
authors.forename: R
authors.initials: R
authors.lastname: Butler
authors.forename: J
authors.initials: J
authors.lastname: Sampson
authors.forename: D T
authors.initials: DT
authors.lastname: Pilz
authors.forename: F
authors.initials: F
authors.lastname: Laccone
authors.forename: A J
authors.initials: AJ
authors.lastname: Clarke
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D018628:Gene Dosage; D005820:Genetic Testing; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D015518:Rett Syndrome / Q000175:diagnosis* / Q000235:genetics*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2