title: Increased MECP2 gene copy number as the result of genomic duplication in neurodevelopmentally delayed males.
abstract: OBJECTIVE
  Mutations in the MECP2 gene are associated with Rett syndrome, an X-linked mental retardation disorder in females. Mutations also cause variable neurodevelopmental phenotypes in rare affected males. Recent clinical testing for MECP2 gene rearrangements revealed that entire MECP2 gene duplication occurs in some males manifesting a progressive neurodevelopmental syndrome.
  
  
  METHODS
  Clinical testing through quantitative DNA methods and chromosomal microarray analysis in our laboratories identified seven male patients with increased MECP2 gene copy number.
  
  
  RESULTS
  Duplication of the entire MECP2 gene was found in six patients, and MECP2 triplication was found in one patient with the most severe phenotype. The Xq28 duplications observed in these males are unique and vary in size from approximately 200 kb to 2.2 Mb. Three of the mothers who were tested were asymptomatic duplication carriers with skewed X-inactivation. In silico analysis of the Xq28 flanking region showed numerous low-copy repeats with potential roles in recombination.
  
  
  CONCLUSIONS
  These collective data suggest that increased MECP2 gene copy number is mainly responsible for the neurodevelopmental phenotypes in these males. These findings underscore the allelic and phenotypic heterogeneity associated with the MECP2 gene and highlight the value of molecular analysis for patient diagnosis, family members at risk, and genetic counseling.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: del Gaudio
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.forename: Fernando
authors.initials: F
authors.lastname: Scaglia
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ward
authors.forename: William J
authors.initials: WJ
authors.lastname: Craigen
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Glaze
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Neul
authors.forename: Ankita
authors.initials: A
authors.lastname: Patel
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lee
authors.forename: Mira
authors.initials: M
authors.lastname: Irons
authors.forename: Susan A
authors.initials: SA
authors.lastname: Berry
authors.forename: Amber A
authors.initials: AA
authors.lastname: Pursley
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Grebe
authors.forename: Debra
authors.initials: D
authors.lastname: Freedenberg
authors.forename: Rick A
authors.initials: RA
authors.lastname: Martin
authors.forename: Gary E
authors.initials: GE
authors.lastname: Hsich
authors.forename: Jena R
authors.initials: JR
authors.lastname: Khera
authors.forename: Neil R
authors.initials: NR
authors.lastname: Friedman
authors.forename: Huda Y
authors.initials: HY
authors.lastname: Zoghbi
authors.forename: Christine M
authors.initials: CM
authors.lastname: Eng
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Roa
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X; D002658:Developmental Disabilities / Q000235:genetics*; D018628:Gene Dosage; D020440:Gene Duplication; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2