A novel mutation in JARID1C/SMCX in a patient with autism spectrum disorder (ASD)

Am J Med Genet A. 2008 Feb 15;146A(4):505-11. doi: 10.1002/ajmg.a.32142.


We describe a nondysmorphic patient with developmental delay and autism spectrum disorder who has a missense mutation in the Jumonji AT-rich interactive domain 1C (JARID1C) gene. This child first presented at 30 months of age with stereotyped and repetitive behaviors, impairment in social reciprocity and in the use of multiple nonverbal behaviors, and developmental delay primarily in the language domain. A diagnosis of autism was made and subsequently confirmed at the current age of 47 months. Cytogenetic and fragile X studies were normal. Mutational analysis revealed a novel missense mutation in exon 16 of the JARID1C gene that results in an arginine to tryptophan substitution at amino acid 766 (R766W). Sequence alignment analysis with multiple available eukaryotic sequences including the homologous proteins of mouse and zebrafish demonstrated that the affected amino acid is conserved. JARID1C has not previously been implicated in autism susceptibility. Recent novel molecular evidence suggests that it is a histone demethylase specific for di- and trimethylated histone 3 lysine 4 (H3K4) and functions as a transcriptional repressor by fostering REST-mediated neuronal gene regulation. The JARID1C-regulated genes SCN2A, CACNA1H, BDNF, and SLC18A1 have previously been associated with autism and cognitive dysfunction. This patient brings the total number of reported JARID1C mutations to 14. This presentation both extends the range of neurocognitive phenotypes attributable to mutations in this gene and illustrates the importance of molecular studies and DNA sequence analysis for accurate diagnosis of monogenic causes of autism.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Autistic Disorder / genetics*
  • Base Sequence
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Pedigree
  • Point Mutation*
  • Retinoblastoma-Binding Protein 2
  • Tumor Suppressor Proteins / genetics*


  • Intracellular Signaling Peptides and Proteins
  • Tumor Suppressor Proteins
  • KDM5A protein, human
  • Retinoblastoma-Binding Protein 2