Genetic and clinical analysis of a large Dutch Gilles de la Tourette family

Verkerk, Annemieke J.M.H.; Cath, Daniëlle C.; Linde, Herma C. van der; Both, J; Heutink, Peter; Breedveld, Guido J.; Aulchenko, Yurii S.; Oostra, Ben A.

doi:10.1038/sj.mp.4001877

Cited by 57 publications

(46 citation statements)

References 46 publications

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“…These two variations could not be identified in several studies of small TS cohorts, large TS families, and in TS patients from population isolates (Deng et al, 2006;Keen-Kim et al, 2006;Verkerk et al, 2006;Chou et al, 2007;Fabbrini et al, 2007;Orth et al, 2007;Zimprich et al, 2008;Miranda et al, 2009). In a cohort of 989 TS patients, var321 was found in the parents of two unrelated TS probands, but not in the probands themselves (Fig.…”

Section: Introductionmentioning

confidence: 75%

“…In a few studies, the contribution of SLITRK1 deletions in TS pathogenesis has been investigated by real-time PCR targeting the SLITRK1 gene (Verkerk et al, 2006;Fabbrini et al, 2007) or by genome-wide analysis of copy number variations (Sundaram et al, 2010;Fernandez et al, 2012). However, none of these studies detected deletion of the SLITRK1 gene in TS patients.…”

Section: Resultsmentioning

confidence: 97%

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

Yasmeen¹,

Melchior²,

Bertelsen

et al. 2013

Psychiatric Genetics

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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.

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Section: Introductionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 97%

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

Yasmeen¹,

Melchior²,

Bertelsen

et al. 2013

Psychiatric Genetics

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show abstract

“…Tourette syndrome (TS) present with a substantial genetic contribution, with no clearly identified genes (Pauls 2003;Robertson and Cavanna 2007;Tourette Syndrome Association International Consortium for Genetics 2007;Verkerk et al 2006;Laurin et al 2009). Hence, emerges the need for discovering neuroendophenotypes that may increase the power to detect quantitative traits influencing behavior and disease liability.…”

Section: Introductionmentioning

confidence: 99%

Thinning of the Motor–Cingulate–Insular Cortices in Siblings Concordant for Tourette Syndrome

et al. 2009

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Fraternal twin studies on normal subjects have demonstrated low heritability (intra-class correlation coefficient) estimates for frontal brain regions (r = 0.43). Here we aimed to investigate the relatedness/similarity estimates of the frontal brain regions in fraternal subjects concordant for Tourette syndrome (TS). We sought to identify regional brain similarities between siblings concordant for TS as an exploratory step towards the identification of potential brain structures involved in the TS phenotype. The identified brain structures may then serve in subsequent molecular genetic and linkage studies. In addition, we regressed cortical thickness and TS clinical severity scores to assess the relation between TS clinical symptoms and cortical structures. Sixteen sibling pairs concordant for TS were scanned using a 1.5 T magnetic resonance imaging scanner (age range 10-25, mean 17.19 +/- 4.1). Brain morphology was assessed using the fully automated Civet pipeline at the Montreal Neurological Institute. TS was assessed using the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), Yale Global Tic Severity Scale (YGTSS) and the Goetz Tic Scale. We report high relatedness/similarity estimates for fraternal siblings concordant for TS (r = 0.86-0.60) in the middle frontal-motor/cingulate/insular cortices. Regression analysis revealed significant negative correlations in the right insula with the YGTSS (r = -0.41, F = 6.09, P < 0.02) and the left cingulated cortex with the (CY-BOCS) (r = -0.35, F = 4.30, P < 0.05). Since previous findings have concluded that normal fraternal siblings are less alike in frontal cortices, the present findings may be attributed to TS. We speculate that the high ICC between siblings and the negative correlation between TS symptoms severity and cortical thickness measurements are related to the disturbances in the maturation of the motor-cingulate-insular cortical neural system that mediate self-regulatory processes. Such delayed maturation may consequently contribute to the development of TS by releasing motor and vocal tics from regulatory control. These findings may have important genetic implications.

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“…The var321 of SLITRK1 altered binding to the microRNA, miR-189, further increasing the negative modulation of SLITRK1 mRNA expression associated with miR-189. However, subsequent studies have been unable to replicate the association of SLITRK1 mutations with GTS in larger populations (Deng et al, 2006;Scharf et al, 2008;Verkerk et al, 2006;Wendland et al, 2006), arguing against co-segregation of SLITRK1 and GTS. Studies with knockout mice have revealed probable associations of Slitrks with neuropsychiatric disorders.…”

Section: Slit and Trk-like Familymentioning

confidence: 99%

The Leucine-Rich Repeat Superfamily of Synaptic Adhesion Molecules: LRRTMs and Slitrks

2012

Molecules and Cells

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Genetic and clinical analysis of a large Dutch Gilles de la Tourette family

Cited by 57 publications

References 46 publications

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

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

Thinning of the Motor–Cingulate–Insular Cortices in Siblings Concordant for Tourette Syndrome

The Leucine-Rich Repeat Superfamily of Synaptic Adhesion Molecules: LRRTMs and Slitrks

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