Sequence analysis of SLITRK1 for var321 in Danish patients with Tourette syndrome and review of the literature

Abstract

Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and vocal tics and is often accompanied by comorbidities such as attention deficit hyperactivity disorder and obsessive-compulsive disorder. The complex etiology of TS and its co-occurrence with other disorders impedes linking genetic changes with disease segregation. One of the few genes that has been linked to TS is the SLITRK1 (Slit and Trk-like 1) gene, where four variations have been suggested as possible disease-associated changes. One of these variations, which has been reported in six unrelated TS patients, was a noncoding variant (var321) at the 3'-untranslated region of SLITRK1 within a conserved binding site for microRNA has-mir-189. To elucidate the potential role of var321 in disease pathogenesis, a cohort of 112 deeply phenotyped Danish TS patients was investigated for this variation. We could not detect var321 in the present cohort, suggesting that this is not a common variant among Danish TS patients.

Analysis of SLITRK1 in Japanese patients with Tourette syndrome using a next-generation sequencer

“…This result may suggest that the varCDfs or the var321 is not a major component of the pathogenesis of TS, which may be consistent with the results of the previous replication studies (Scharf et al, 2008;Keen-Kim et al, 2006;Wendland et al, 2006;Yasmeen et al, 2013).…”

“…A larger sample size might be needed to identify the two variants or to observe a significant association of each SNP or haplotype with the disease. To date, in 1582 TS patients, seven with the var321 and one with the varCDfs have been identified in total, which means that more than 200 patients might be needed to detect one of the variants by simple calculation (Abelson et al, 2005;Keen-Kim et al, 2006;Scharf et al, 2008;Yasmeen et al, 2013). Second, in the sequence analysis, sufficient depth of coverage was not obtained in some patients in part of the 5′-UTR and 3′-UTR, which resulted in the incomplete sequence of the two regions.…”

“…To our knowledge, a total of nine TS families with the var321 have been reported in the literature to date, whereas the variant was not transmitted to their affected children in the four families (Abelson et al, 2005;Keen-Kim et al, 2006;Scharf et al, 2008;Yasmeen et al, 2013). In addition, the presence of the var321 was observed in two healthy controls (Keen-Kim et al, 2006;Wendland et al, 2006), which suggested the possibility that the variant might be neutral rather than disease related.…”

“…In addition, the presence of the var321 was observed in two healthy controls (Keen-Kim et al, 2006;Wendland et al, 2006), which suggested the possibility that the variant might be neutral rather than disease related. The varCDfs has not been detected in the replication studies (Keen-Kim et al, 2006;Yasmeen et al, 2013). Miranda et al (2009) first carried out an association analysis between TS and the three single nucleotide polymorphisms (SNPs), rs9546538, rs9531520, and rs9593835, tagging the major haplotypes of the gene.…”

Human diseases caused by germline and somatic abnormalities in microRNA and microRNA‐related genes

“…; Yasmeen et al. ). Furthermore, the variant was found in one individual without a history of tics or obsessive behaviors (Keen‐Kim et al.…”