Gonadal mosaicism in ARID1B gene causes intellectual disability and dysmorphic features in three siblings

Am J Med Genet A. 2016 Jan;170A(1):156-61. doi: 10.1002/ajmg.a.37405. Epub 2015 Sep 23.


The gene encoding the AT-rich interaction domain-containing protein 1B (ARID1B) has recently been shown to be one of the most frequently mutated genes in patients with intellectual disability (ID). The phenotypic spectrums associated with variants in this gene vary widely ranging for mild to severe non-specific ID to Coffin-Siris syndrome. In this study, we evaluated three children from a consanguineous Emirati family affected with ID and dysmorphic features. Genomic DNA from all affected siblings was analyzed using CGH array and whole-exome sequencing (WES). Based on a recessive mode of inheritance, homozygous or compound heterozygous variants shared among all three affected children could not be identified. However, further analysis revealed a heterozygous variant (c.4318C>T; p.Q1440*) in the three affected children in an autosomal dominant ID causing gene, ARID1B. This variant was absent in peripheral blood samples obtained from both parents and unaffected siblings. Therefore, we propose that the most likely explanation for this situation is that one of the parents is a gonadal mosaic for the variant. To the best of our knowledge, this is the first report of a gonadal mosaicism inheritance of an ARID1B variant leading to familial ID recurrence.

Keywords: ARID1B; gonadal mosaicism; non-Mendelian inheritance; whole-exome sequencing.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Child
  • DNA-Binding Proteins / genetics*
  • Exome / genetics*
  • Face / abnormalities*
  • Face / pathology
  • Female
  • Hand Deformities, Congenital / genetics*
  • Hand Deformities, Congenital / pathology
  • Heterozygote
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Micrognathism / genetics*
  • Micrognathism / pathology
  • Mosaicism*
  • Mutation / genetics*
  • Neck / abnormalities*
  • Neck / pathology
  • Pedigree
  • Siblings
  • Transcription Factors / genetics*


  • ARID1B protein, human
  • DNA-Binding Proteins
  • Transcription Factors

Supplementary concepts

  • Coffin-Siris syndrome