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Functional SLITRK1 var321, varCDfs and SLC6A4 G56A variants and susceptibility to obsessive-compulsive disorder

Molecular Psychiatry volume 11, pages 802–804 (2006)Cite this article

Recent reports provide evidence for a role of SLITRK1 in Tourette's syndrome (TS) with obsessive-compulsive (OC) symptoms and for the G56A serotonin transporter gene (SLC6A4) variant in autism.1, 2 Here, we investigated these gene variants in obsessive-compulsive disorder (OCD), based on high degrees of TS/OCD comorbidity, plus G56A functionally resembling SLC6A4 I425 V in producing transporter gain-of-function.2, 3, 4

SLITRK1 was uncovered as a candidate for TS owing to its <230 kb proximity to a breakpoint of a 13q chromosomal inversion found in a child with TS and attention-deficit/hyperactivity disorder (ADHD), in addition to its role in neurite outgrowth.1 Furthermore, screening of 174 additional TS probands for SLITRK1 variants revealed a truncating frameshift mutation, varCDfs, with complete loss of function in one, and a microRNA domain-affecting variant, var321, which leads to reduced reporter gene activity in vitro, in two other of these probands (Table 1).1

Table 1 Oligonucleotide primer and probe sequences of 5′-exonuclease genotyping assays.
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Acknowledgements

We thank Dr Matthew State, Yale University, for kindly providing amplified genomic DNA of var321 and varCDfs heterozygotes. This research was supported by the Intramural Research Program of the NIMH, NIH.

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  1. Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD, USA

    J R Wendland, M R Kruse & D L Murphy

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Wendland, J., Kruse, M. & Murphy, D. Functional SLITRK1 var321, varCDfs and SLC6A4 G56A variants and susceptibility to obsessive-compulsive disorder. Mol Psychiatry 11, 802–804 (2006). https://doi.org/10.1038/sj.mp.4001848

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