Skip to main content

Advertisement

SpringerLink
Log in

The G22A Polymorphism of the ADA Gene and Susceptibility to Autism Spectrum Disorders

  • Original Paper
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Inborn errors of purine metabolism have been implicated as a cause for some cases of autism. This hypothesis is supported by the finding of decreased adenosine deaminase (ADA) activity in the sera of some children with autism and reports of an association of the A allele of the ADA G22A (Asp8Asn) polymorphism in individuals with autism of Italian-descent. We tested the ADA G22A polymorphism in 126 North American affected sib-pair families but found no aberrant allele distributions in cases versus controls. Instead, we found an increased transmission of the G allele from fathers to affected children. Our findings suggest that the ADA G22A polymorphism plays a minimal role in susceptibility to autism in North American families.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Battistuzzi, G., Iudicone, P., Santolamazza, P., & Petrucci, R. (1981). Activity of adenosine deaminase allelic forms in intact erythrocytes and in lymphocytes. Annals of Human Genetics, 45, 15–19.

    Article  PubMed  CAS  Google Scholar 

  • Bottini, N., De Luca, D., Saccucci, P., Fiumara, A., Elia, M., Porfirio, M. C., et al. (2001). Autism: evidence of association with adenosine deaminase genetic polymorphism. Neurogenetics, 3, 111–113.

    Article  PubMed  CAS  Google Scholar 

  • Chakrabarti, S., & Fombonne, E. (2005). Pervasive developmental disorders in preschool children: confirmation of high prevalence. American Journal of Psychiatry, 162, 1133–1141.

    Article  PubMed  Google Scholar 

  • Coleman, M., Landgrebe, M. A., & Landgrebe, A. R. (1976). Purine autism. Hyperuricosuria in autistic children: does this identify a subgroup of autism? In M. Coleman (Eds.), The autistic syndromes (pp. 183–214). New York: Elsevier.

    Google Scholar 

  • Evans, H. K., Wylie, A. A., Murphy, S. K., & Jirtle, R. L. (2001). The neuronatin gene resides in a ‘micro-imprinted’ domain on human chromosome 20q11.2. Genomics, 77, 99–104.

    Article  PubMed  CAS  Google Scholar 

  • Geschwind, D. H., Sowinski, J., Lord, C., Iversen, P., Shestack, J., Jones, P., et al. (2001). The autism genetic resource exchange: a resource for the study of autism and related neuropsychiatric conditions. American Journal of Human Genetics, 69, 463–466.

    Article  PubMed  CAS  Google Scholar 

  • Hayward, B. E., Kamiya, M., Strain, L., Moran, V., Campbell, R., Hayashizaki, Y., et al. (1998). The human GNAS1 gene is imprinted and encodes distinct paternally and biallelically expressed G proteins. Proceedings of the National Academy of Sciences of the United States of America, 95, 10038–10043.

    Article  PubMed  CAS  Google Scholar 

  • Hirschhorn, R., Yang, D. R., & Israni, A. (1994). An Asp8Asn substitution results in the adenosine deaminase (ADA) genetic polymorphism (ADA 2 allozyme): occurrence on different chromosomal backgrounds and apparent intragenic crossover. Annals of Human Genetics, 58, 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Korvatska, E., Van de Water, J., Anders, T. F., & Gershwin, M. E. (2002). Genetic and immunologic considerations in autism. Neurobiology of Disease, 9, 107–125.

    Article  PubMed  CAS  Google Scholar 

  • Laird, N., Horvath, S., & Xu, X. (2000). Implementing a unified approach to family based tests of association. Genetic Epidemiology, 19(Suppl1), S36–S42.

    Article  PubMed  Google Scholar 

  • Lander, E. S. (1996). The new genomics: global views of biology. Science, 274, 536–539.

    Article  PubMed  CAS  Google Scholar 

  • Lord, C., Rutter, M., Goode, S., Heemsbergen, J., Jordan, H., Mawhood, L., et al. (1989). Autism Diagnostic Observation Schedule: a standardized observation of communicative and social behavior. Journal of Autism and Developmental Disorders, 19, 185–212.

    Article  PubMed  CAS  Google Scholar 

  • Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism Diagnostic Interview-Revised: a revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24, 659–685.

    Article  PubMed  CAS  Google Scholar 

  • Nowell, M. A., Hackney, D. B., Muraki, A. S., & Coleman, M. (1990). Varied MR appearance of autism: fifty-three pediatric patients having the full autistic syndrome. Magnetic Resonance Imaging, 8, 811–816.

    Article  PubMed  CAS  Google Scholar 

  • Nyhan, W. L., James, J. A., Teberg, A. J., Sweetman, L., & Nelson, L.G. (1969). A new disorder of purine metabolism with behavioral manifestations. The Journal of Pediatrics, 74, 20–27.

    Article  PubMed  CAS  Google Scholar 

  • Page, T., & Coleman, M. (2000). Purine metabolism abnormalities in a hyperuricosuric subclass of autism. Biochimica et Biophysica Acta, 1500, 291–296.

    PubMed  CAS  Google Scholar 

  • Page, T., & Moseley, C. (2002). Metabolic treatment of hyperuricosuric autism. Progress in Neuro-psychopharmacology and Biological Psychiatry, 26, 397–400.

    Article  PubMed  Google Scholar 

  • Persico, A. M., Militerni, R., Bravaccio, C., Schneider, C., Melmed, R., Trillo, S., et al. (2000). Adenosine deaminase alleles and autistic disorder: Case-control and family-based association studies. American Journal of Medical Genetics, 96, 784–790.

    Article  PubMed  CAS  Google Scholar 

  • Peters, J., & Beechey, C. (2004). Identification and characterisation of imprinted genes in the mouse. Briefings in Functional Genomics and Proteomics, 2, 320–333.

    Article  PubMed  CAS  Google Scholar 

  • Resta, R., & Thompson, L. F. (1997). SCID: the role of adenosine deaminase deficiency. Immunology Today, 18, 371–374.

    Article  PubMed  CAS  Google Scholar 

  • Robinson, P. D., Schutz, C. K., Macciardi, F., White, B. N., & Holden, J. J. A. (2001). Genetically determined low levels of maternal serum dopamine beta-hydroxylase and the etiology of autism spectrum disorders. American Journal of Medical Genetics, 100, 30–36.

    Article  PubMed  CAS  Google Scholar 

  • Sham, P. C., & Curtis, D. (1995). An extended transmission/disequilibrium test (TDT) for multi-allele marker loci. Annals of Human Genetics, 59, 323–336.

    Article  PubMed  CAS  Google Scholar 

  • Singh, V. K., Warren, R., Averett, R., & Ghaziuddin, M. (1997). Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatric Neurology, 17, 88–90.

    Article  PubMed  CAS  Google Scholar 

  • Stathis, S. L., Cowley, D. M., & Broe, D. (2000). Autism and adenylosuccinase deficiency. Journal of the American Academy of Child and Adolescent Psychiatry, 39, 274–275.

    Article  PubMed  CAS  Google Scholar 

  • Stone, R. L., Aimi, J., Barshop, B. A., Jaeken, J., Van den Berghe, G., Zalkin, H., et al. (1992). A mutation in adenylosuccinate lyase associated with mental retardation and autistic features. Nature Genetics, 1, 59–63.

    Article  PubMed  CAS  Google Scholar 

  • Stubbs, G., Litt, M., Lis, E., Jackson, R., Voth, W., Lindberg, A., et al. (1982). Adenosine deaminase activity decreased in autism. Journal of the American Academy of Child Psychiatry, 21, 71–74.

    PubMed  CAS  Google Scholar 

  • Trottier, G., Srivastava, L., & Walker, C-D. (1999). Etiology of infantile autism: a review of recent advances in genetic and neurobiological research. Journal of Psychiatry & Neuroscience, 24, 103–115.

    CAS  Google Scholar 

  • Van Steen, K., & Laird, N. M. (2004). Family-based association tests and the FBAT-toolkit. User’s manual. Retrieved January 28, 2006, from http://www.biostat.harvard.edu/∼fbat/manual.mar4.doc

  • Weissmann, J., Volmer, M., & Pribilla, O. (1982). Survey of the distribution of adenosine deaminase and superoxide dismutase markers in different populations. Human Heredity, 32, 344–356.

    Article  PubMed  CAS  Google Scholar 

  • Zoroglu, S. S., Armutcu, F., Ozen, S., Gurel, A., Sivasli, E., Yetkin, O., et al. (2004). Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. European Archives of Psychiatry and Clinical Neuroscience, 254, 143–147.

    PubMed  Google Scholar 

Download references

Acknowledgments

The authors are very grateful to the families who participated in this research and we gratefully acknowledge the resources provided by the Autism Genetic Resource Exchange (AGRE) Consortium and the participating AGRE families. The Autism Genetic Resource Exchange is a program of Cure Autism Now and is supported, in part, by grant MH64547 from the National Institute of Mental Health to Daniel H. Geschwind (PI).

This work was supported by research grants from the Ontario Mental Health Foundation (to JJAH) and the Canadian Institutes for Health Research (#43820) to the Autism Spectrum Disorders Canadian-American Research Consortium (ASD-CARC) (JJAH, PI; www.asdcarc.com; www.autismresearch.ca) and a research studentship from the Ontario Mental Health Foundation to JAH. JAH is a trainee with the CIHR/NAAR STIHR Interdisciplinary Inter-Institute Autism Spectrum Disorders Training Program (PI: JJAH).

Author information

Authors and Affiliations

  1. Department of Physiology, Queen’s University, Kingston, ON, Canada

    Joe A. Hettinger & Jeanette Jeltje Anne Holden

  2. Department of Psychiatry, Queen’s University, Kingston, ON, Canada

    Xudong Liu & Jeanette Jeltje Anne Holden

  3. Centre for Neuroscience Studies, Queen’s University, Kingston, ON, Canada

    Jeanette Jeltje Anne Holden

  4. Autism Research Program, Ongwanada Resource Centre, 191 Portsmouth Ave., Kingston, ON, Canada, K7M 8A6

    Joe A. Hettinger, Xudong Liu & Jeanette Jeltje Anne Holden

  5. Autism Spectrum Disorders, Canadian-American Research Consortium, Kingston, ON, Canada

    Xudong Liu & Jeanette Jeltje Anne Holden

Authors
  1. Joe A. Hettinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xudong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jeanette Jeltje Anne Holden
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeanette Jeltje Anne Holden.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hettinger, J.A., Liu, X. & Holden, J.J.A. The G22A Polymorphism of the ADA Gene and Susceptibility to Autism Spectrum Disorders. J Autism Dev Disord 38, 14–19 (2008). https://doi.org/10.1007/s10803-006-0354-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-006-0354-0

Keywords

Search

Navigation