1. ¹Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology, Catholic University of Leuven, Leuven, Belgium
2. ²Centre for Human Genetics, Division of Clinical Genetics, Catholic University of Leuven, Leuven, Belgium
3. ³Laboratory for Molecular Oncology, Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology, Catholic University of Leuven, Leuven, Belgium
4. ⁴Department of Child Psychiatry, Catholic University of Leuven, Leuven, Belgium
5. ⁵Centre for Clinical Genetics, University of Maastricht, Maastricht, The Netherlands

Correspondence: Professor K Devriendt, Centre for Human Genetics, Herestraat 49, Leuven B-3000, Belgium. Tel: +32 16 34 59 03; Fax: +32 16 34 60 51; E-mail: koen.devriendt@med.kuleuven.be

Received 11 August 2006; Revised 30 December 2006; Accepted 5 January 2007; Published online 7 February 2007.

Abstract

Autism is a genetic neurodevelopmental disorder of unknown cause and pathogenesis. The identification of genes involved in autism is expected to increase our understanding of its pathogenesis. Infrequently, neurodevelopmental disorders like autism are associated with chromosomal anomalies. To identify candidate genes for autism, we initiated a positional cloning strategy starting from individuals with idiopathic autism carrying a de novo chromosomal anomaly. We report on the clinical, cytogenetic and molecular findings in a male person with autism, no physical abnormalities and normal IQ, carrying a de novo balanced paracentric inversion 46,XY,inv(10)(q11.1;q21.3). The distal breakpoint disrupts the TRIP8 gene, which codes for a protein predicted to be a transcriptional regulator associated with nuclear thyroid hormone receptors. However, no link between thyroid gland and autism has been reported so far. In addition, the same breakpoint abolishes expression of a nearby gene, REEP3, through a position effect. Receptor Expression-Enhancing Proteins (REEP) 3 is one of the six human homologs of yeast Yop1p, a probable regulator of cellular vesicle trafficking between the endoplasmatic reticulum and the Golgi network. These observations suggest that TRIP8 and REEP3 are both positional candidate genes for autism. In addition, our data indicate that in the selection of positional candidate genes when studying chromosomal aberrations, position effects should be taken into account.