Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability

Eur J Hum Genet. 2014 Feb;22(2):289-92. doi: 10.1038/ejhg.2013.113. Epub 2013 May 15.


Intellectual disability (ID) is frequent in the general population, with 1 in 50 individuals directly affected worldwide. The multiple etiologies include X-linked ID (XLID). Among syndromic XLID, few syndromes present severe ID associated with postnatal microcephaly and midline stereotypic hand movements. We report on three male patients with ID, midline stereotypic hand movements, hypotonia, hyperkinesia, strabismus, as well as seizures (2/3), and non-inherited and postnatal onset microcephaly (2/3). Using array CGH and exome sequencing we characterised two truncating mutations in IQSEC2, namely two de novo intragenic duplication mapped to the Xp11.22 region and a nonsense mutation in exon 7. We propose that truncating mutations in IQSEC2 are responsible for syndromic severe ID in male patients and should be screened in patients without mutations in MECP2, FOXG1, CDKL5 and MEF2C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / diagnosis*
  • Abnormalities, Multiple / genetics
  • Adult
  • Child, Preschool
  • Codon, Nonsense
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Intellectual Disability / classification
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics
  • Male
  • Phenotype


  • Codon, Nonsense
  • Guanine Nucleotide Exchange Factors
  • IQSEC2 protein, human