Concomitant Microduplications of MECP2 and ATRX in Male Patients With Severe Mental Retardation

J Hum Genet. 2012 Jan;57(1):73-7. doi: 10.1038/jhg.2011.131. Epub 2011 Dec 1.

Abstract

Investigations of chromosomal rearrangements in patients with mental retardation (MR) are particularly informative in the search for genes involved in MR. Here we report a family with concomitant duplications of methyl CpG binding protein 2 (MECP2) at Xq28 and ATRX (the causative gene for X-linked alpha thalassemia/mental retardation) at Xq21.1 detected by array-comparative genomic hybridization. The alterations were observed in a 25-year-old man who inherited them from his mother, who showed a normal phenotype and completely skewed X-chromosome inactivation, and also in his cousin, a 32-year-old man. The proband and his cousin showed severe MR, muscular hypotonia, recurrent respiratory infections and various other features characteristic of MECP2 duplication syndrome. However, the proband also had cerebellar atrophy never reported before in MECP2 duplication syndrome, suggesting that his phenotypes were modified through the ATRX duplication in an additive or epistatic manner.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Helicases / genetics*
  • DNA Methylation / genetics
  • DNA, Ribosomal / genetics
  • Female
  • Gene Dosage / genetics
  • Gene Duplication / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Male
  • Methyl-CpG-Binding Protein 2 / genetics*
  • Nuclear Proteins / genetics*
  • Pedigree
  • Phenotype
  • X-linked Nuclear Protein

Substances

  • DNA, Ribosomal
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Nuclear Proteins
  • DNA Helicases
  • ATRX protein, human
  • X-linked Nuclear Protein