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Genetic determinants of autism in individuals with deletions of 18q

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Abstract

Previous research has suggested that individuals with constitutional hemizygosity of 18q have a higher risk of autistic-like behaviors. We sought to identify genomic factors located on chromosome 18 as well as other loci that correlate with autistic behaviors. One hundred and five individuals with 18q- were assessed by high-resolution oligo aCGH and by parental ratings of behavior on the Gilliam Autism Rating Scale. Forty-five individuals (43%) had scores within the “possibly” or “very likely” categories of risk for an autism diagnosis. We searched for genetic determinants of autism by (1) identifying additional chromosome copy number changes (2) Identifying common regions of hemizygosity on 18q, and (3) evaluating four regions containing candidate genes located on 18q (MBD1, TCF4, NETO1, FBXO15). Three individuals with a “very likely” probability of autism had a captured 17p telomere in addition to the 18q deletion suggesting a possible synergy between hemizygosity of 18q and trigosity of 17p. In addition, two of the individuals with an 18q deletion and a “very likely” probability of autism rating had a duplication of the entire short arm of chromosome 18. Although no common region of hemizygosity on 18q was identified, analysis of four regions containing candidate genes suggested that individuals were significantly more likely to exhibit autistic-like behaviors if their region of hemizygosity included TCF4, NETO1, and FBXO15 than if they had any other combination of hemizygosity of the candidate genes. Taken together, these findings identify several new potential candidate genes or regions for autistic behaviors.

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Acknowledgments

We would like to thank the families who have so generously supported this work with their time and enthusiasm. This work was supported by the MacDonald family, The Chromosome 18 Registry & Research Society and NIH/NICHD grant R01-HD-045907.

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Authors and Affiliations

  1. Department of Pediatrics, UT Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Louise O’Donnell, Bridgette Soileau, Patricia Heard, Erika Carter, Courtney Sebold, Daniel E. Hale & Jannine D. Cody

  2. Department of Psychiatry, UT Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Louise O’Donnell

  3. Department of Epidemiology and Biostatistics, UT Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Jon Gelfond

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  1. Louise O’Donnell
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  2. Bridgette Soileau
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Correspondence to Jannine D. Cody.

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O’Donnell, L., Soileau, B., Heard, P. et al. Genetic determinants of autism in individuals with deletions of 18q. Hum Genet 128, 155–164 (2010). https://doi.org/10.1007/s00439-010-0839-y

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  • DOI: https://doi.org/10.1007/s00439-010-0839-y

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