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.
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Acknowledgements
We thank the patient and his family for their cooperation. The excellent technical assistance of Reinhilde Thoelen performing the FISH analyses is gratefully acknowledged. We would like to thank Marijke Bauters for her very kind assistance on real-time PCR and Bernard Thienpont for performing the aCGH analysis on the proband. This work is supported by a grant from Interuniversitary Attraction Poles (IAP-P5/25, Belgian State), from Geconcerteerde Onderzoeksacties (GOA2002/010, Belgium) and from the Fund for Scientific Research-Flanders (FWO G0264.04, Belgium). KD is a Senior Clinical Investigator of FWO.
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Castermans, D., Vermeesch, J., Fryns, JP. et al. Identification and characterization of the TRIP8 and REEP3 genes on chromosome 10q21.3 as novel candidate genes for autism. Eur J Hum Genet 15, 422–431 (2007). https://doi.org/10.1038/sj.ejhg.5201785
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DOI: https://doi.org/10.1038/sj.ejhg.5201785
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