Sporadic male patients with intellectual disability: contribution of X-chromosome copy number variants

Eur J Med Genet. 2012 Nov;55(11):577-85. doi: 10.1016/j.ejmg.2012.05.005. Epub 2012 May 30.


Genome-wide array comparative genome hybridization has become the first in line diagnostic tool in the clinical work-up of patients presenting with intellectual disability. As a result, chromosome X-copy number variations are frequently being detected in routine diagnostics. We retrospectively reviewed genome wide array-CGH data in order to determine the frequency and nature of chromosome X-copy number variations (X-CNV) in a cohort of 2222 sporadic male patients with intellectual disability (ID) referred to us for diagnosis. In this cohort, 68 males were found to have at least one X-CNV (3.1%). However, correct interpretation of causality remains a challenging task, and is essential for proper counseling, especially when the CNV is inherited. On the basis of these data, earlier experience and literature data we designed and propose an algorithm that can be used to evaluate the clinical relevance of X-CNVs detected in sporadic male ID patients. Applied to our cohort, 19 male ID patients (0.85%) were found to carry a (likely) pathogenic X-CNV.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Chromosomes, Human, X / genetics*
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations*
  • Genetic Counseling
  • Genetic Loci
  • Genome, Human
  • Humans
  • Infant
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics*
  • Male
  • Middle Aged
  • Retrospective Studies