The RBMX gene as a candidate for the Shashi X-linked intellectual disability syndrome

Clin Genet. 2015 Oct;88(4):386-90. doi: 10.1111/cge.12511. Epub 2014 Dec 5.


A novel X-linked intellectual disability (XLID) syndrome with moderate intellectual disability and distinguishing craniofacial dysmorphisms had been previously mapped to the Xq26-q27 interval. On whole exome sequencing in the large family originally reported with this disorder, we identified a 23 bp frameshift deletion in the RNA binding motif protein X-linked (RBMX) gene at Xq26 in the affected males (n = 7), one carrier female, absent in unaffected males (n = 2) and in control databases (7800 exomes). The RBMX gene has not been previously causal of human disease. We examined the genic intolerance scores for the coding regions and the non-coding regions of RBMX; the findings were indicative of RBMX being relatively intolerant to loss of function variants, a distinctive pattern seen in a subset of XLID genes. Prior expression and animal modeling studies indicate that loss of function of RBMX results in abnormal brain development. Our finding putatively adds a novel gene to the loci associated with XLID and may enable the identification of other individuals affected with this distinctive syndrome.

Keywords: Shashi syndrome; X-linked intellectual disability; X-linked mental retardation; whole exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • DNA Mutational Analysis
  • Exome*
  • Female
  • Genetic Association Studies
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics*
  • Humans
  • Male
  • Mental Retardation, X-Linked / genetics*
  • Middle Aged
  • Pedigree


  • Heterogeneous-Nuclear Ribonucleoproteins
  • RBMX protein, human

Supplementary concepts

  • Orofaciodigital syndrome, Shashi type