Association between autism spectrum disorder in individuals with velocardiofacial (22q11.2 deletion) syndrome and PRODH and COMT genotypes

Petya Radoeva, Ioana Coman, Cynthia Salazar, Karen Gentile, Anne Higgins, Frank Middleton, Kevin Antshel, Wanda Fremont, Robert Shprintzen, Bernice Morrow, Wendy Kates

18 Scopus citations


Velocardiofacial (VCFS; 22q11.2 deletion) syndrome is a genetic disorder that results from a hemizygous deletion of the q11.2 region on chromosome 22, and is associated with greatly increased risk for psychiatric disorders, including autism spectrum disorder (ASD) and schizophrenia. There is emerging evidence for the involvement of catechol-O-methyltransferase (COMT) and proline dehydrogenase (oxidase) 1 (PRODH) in the psychiatric phenotype of individuals with VCFS. Here, we tested the hypothesis that PRODH and COMT are associated with ASD in youths with VCFS. We found that individuals with VCFS and the low-activity alleles of both PRODH and COMT (rs4819756A and rs4680A) were more likely to present with ASD as compared with individuals with VCFS and the high-activity alleles of these genes [P<0.05; odds ratio=6.0 (95% confidence interval=1.27-28.26; N=87)]. Our results suggest that PRODH and COMT may interact to contribute to the ASD phenotype in individuals with VCFS.



  • 22q11.2 deletion
  • autism spectrum disorder
  • catechol-O-methyltransferase
  • proline dehydrogenase
  • velocardiofacial syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Psychiatry and Mental health
  • Biological Psychiatry

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