X-linked intellectual disability update 2017

Am J Med Genet A. 2018 Jun;176(6):1375-1388. doi: 10.1002/ajmg.a.38710. Epub 2018 Apr 25.


The X-chromosome comprises only about 5% of the human genome but accounts for about 15% of the genes currently known to be associated with intellectual disability. The early progress in identifying the X-linked intellectual disability (XLID)-associated genes through linkage analysis and candidate gene sequencing has been accelerated with the use of high-throughput technologies. In the 10 years since the last update, the number of genes associated with XLID has increased by 96% from 72 to 141 and duplications of all 141 XLID genes have been described, primarily through the application of high-resolution microarrays and next generation sequencing. The progress in identifying genetic and genomic alterations associated with XLID has not been matched with insights that improve the clinician's ability to form differential diagnoses, that bring into view the possibility of curative therapies for patients, or that inform scientists of the impact of the genetic alterations on cell organization and function.

Keywords: X-chromosome; XLID; genes; intellectual disability; syndrome.

Publication types

  • Review

MeSH terms

  • Antigens, Nuclear / genetics
  • Cell Cycle Proteins
  • Chromosomes, Human, X
  • Gene Duplication
  • Genes, X-Linked*
  • Genetic Testing / methods
  • Humans
  • Intellectual Disability / genetics*
  • Methyl-CpG-Binding Protein 2
  • Myelin Proteolipid Protein / genetics
  • Phosphoric Monoester Hydrolases / genetics
  • Tumor Suppressor Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics


  • Antigens, Nuclear
  • Cell Cycle Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • Myelin Proteolipid Protein
  • PLP1 protein, human
  • STAG2 protein, human
  • Tumor Suppressor Proteins
  • HUWE1 protein, human
  • Ubiquitin-Protein Ligases
  • Phosphoric Monoester Hydrolases
  • OCRL protein, human