A new syndrome of intellectual disability with dysmorphism due to TBL1XR1 deletion

Am J Med Genet A. 2015 Jan;167A(1):164-8. doi: 10.1002/ajmg.a.36759. Epub 2014 Nov 25.

Abstract

We report here on an 8-year-old girl and her mother, both displaying similar facial dysmorphism, speech delay, and mild to moderate intellectual disability. Array-CGH studies revealed the same interstitial 3q26.32 microdeletion encompassing a single coding gene, TBL1XR1, in both patients. The TBL1XR1 protein, which has four WD40 repeats, has been shown to bind the nuclear corepressor (NCOR) and histone deacetylase-3 complexes (HDAC3). TBL1XR1 mutations have recently been implicated in autism spectrum disorders, but our patients displayed no autistic behavior. Our findings suggest that TBL1XR1 haploinsufficiency can cause intellectual disability with a recognizable dysmorphism, without necessarily causing autistic behavior.

Keywords: 3q26 deletion; TBL1XR1; array comparative genomic hybridization; intellectual disability.

Publication types

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

MeSH terms

  • Adult
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 3 / genetics
  • Comparative Genomic Hybridization
  • Facies*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Intellectual Disability / genetics*
  • Nuclear Proteins / genetics*
  • Pregnancy
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Repressor Proteins / genetics*
  • Syndrome

Substances

  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • TBL1XR1 protein, human