Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene

Mol Psychiatry. 2003 Nov;8(11):916-24. doi: 10.1038/


The results from several genome scans indicate that chromosome 2q21-q33 is likely to contain an autism susceptibility locus. We studied the potential contribution of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP-GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and association analysis using intragenic single nucleotide polymorphisms did not provide evidence for a major role in the aetiology of autism. Four rare nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These variants were present in five families, where they segregate with the autistic phenotype, and were not observed in control individuals. The significance of these variants is unclear, as their low frequency in IMGSAC families does not account for the relatively strong linkage signal at the 2q locus. Further studies are needed to clarify the contribution of cAMP-GEFII gene variants to autism susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autistic Disorder / genetics*
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Chromosomes, Human, Pair 2*
  • Cyclic AMP / metabolism*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genetic Variation
  • Genotype
  • Guanine Nucleotide Exchange Factors / genetics*
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Linkage Disequilibrium
  • Male
  • Mice
  • Mutation, Missense
  • Pedigree
  • Polymorphism, Single Nucleotide


  • Carrier Proteins
  • Guanine Nucleotide Exchange Factors
  • RAPGEF4 protein, human
  • Rapgef4 protein, mouse
  • Cyclic AMP