Gilles de la Tourette syndrome

Selvini, Claudia; Cavanna, Stefano; Cavanna, Andrea E.

doi:10.1016/b978-0-12-813796-3.00015-8

Cited by 3 publications

(3 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The phenotype may be influenced by numerous factors, including environmental, prenatal and perinatal ones, hormonal disturbances, as well as psychosocial stressors [ 3 , 4 , 5 , 6 ]. The clinical phenotype of GTS belongs to a broader entity of tic disorders (TDs) [ 7 ]. The prevalence of GTS in the general pediatric population ranges from 0.3% to 0.77% and is 10–100 fold lower in adulthood, but TDs are more common affecting up to 5% of the general population [ 2 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome

Fichna,

Chiliński,

Halder

et al. 2024

IJMS

View full text Add to dashboard Cite

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental psychiatric disorder with complex and elusive etiology with a significant role of genetic factors. The aim of this study was to identify structural variants that could be associated with familial GTS. The study group comprised 17 multiplex families with 80 patients. Structural variants were identified from whole-genome sequencing data and followed by co-segregation and bioinformatic analyses. The localization of these variants was used to select candidate genes and create gene sets, which were subsequently processed in gene ontology and pathway enrichment analysis. Seventy putative pathogenic variants shared among affected individuals within one family but not present in the control group were identified. Only four private or rare deletions were exonic in LDLRAD4, B2M, USH2A, and ZNF765 genes. Notably, the USH2A gene is involved in cochlear development and sensory perception of sound, a process that was associated previously with familial GTS. In addition, two rare variants and three not present in the control group were co-segregating with the disease in two families, and uncommon insertions in GOLM1 and DISC1 were co-segregating in three families each. Enrichment analysis showed that identified structural variants affected synaptic vesicle endocytosis, cell leading-edge organization, and signaling for neurite outgrowth. The results further support the involvement of the regulation of neurotransmission, neuronal migration, and sound-sensing in GTS.

show abstract

Section: Introductionmentioning

confidence: 99%

Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome

Fichna,

Chiliński,

Halder

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…The clinical phenotype of Tourette syndrome belongs to the spectrum of tic disorders. 1 Moreover, most patients with Tourette syndrome present a variety of additional symptoms due to psychiatric comorbidities, including attention-deficit/hyperactivity disorder (ADHD), obsessive–compulsive disorder (OCD), autism spectrum disorder (ASD), affective disorders, anxiety disorders, impulse control disorders and personality disorders, implying an overlapping etiology. 2 , 3 The tics usually emerge around the age of 4–6 years and are most severe after 5 years, albeit most cases improve during adolescence.…”

Section: Introductionmentioning

confidence: 99%

Genomic variants and inferred biological processes in multiplex families with Tourette syndrome

Fichna

Borczyk

Piechota

et al. 2023

jpn

View full text Add to dashboard Cite

Background: Tourette syndrome is a developmental neuropsychiatric disorder. Its etiology is complex and elusive, although an important role of genetic factors has been established. The aim of the present study was to identify the genomic basis of Tourette syndrome in a group of families with affected members in 2 or 3 generations. Methods: Whole-genome sequencing was performed followed by co-segregation and bioinformatic analyses. Identified variants were used to select candidate genes, which were then subjected to gene ontology and pathway enrichment analysis. Results: The study group included 17 families comprising 80 patients with Tourette syndrome and 44 healthy family members. Co-segregation analysis and subsequent prioritization of variants pinpointed 37 rare and possibly pathogenic variants shared among affected individuals within a single family. Three such variants, in the ALDH2 , DLD and ALDH1B1 genes, could influence oxidoreductase activity in the brain. Two variants, in SLC17A8 and BSN genes, were involved in sensory processing of sound by inner hair cells of the cochlea. Enrichment analysis of genes whose rare variants were present in all patients from at least 2 families identified significant gene sets implicated in cell–cell adhesion, cell junction assembly and organization, processing of sound, synapse assembly, and synaptic signalling processes. Limitations: We did not examine intergenic variants, but they still could influence clinical phenotype. Conclusion: Our results provide a further argument for a role of adhesion molecules and synaptic transmission in neuropsychiatric diseases. Moreover, an involvement of processes related to oxidative stress response and sound-sensing in the pathology of Tourette syndrome seems likely.

show abstract

“…Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by multiple motor and at least one vocal and/or phonic tic which persists for longer than 12 months. The clinical phenotype of GTS belongs to the spectrum of tic disorders (TDs), a broad diagnostic category that includes: Chronic Motor Tic Disorder, Chronic Vocal Tic Disorder, Provisional Tic Disorder, Other Specified Tic Disorder and Unspecified Tic Disorder (Selvini, Cavanna, and Cavanna 2019). In about 90% of cases, GTS is accompanied by comorbid psychiatric disorders, including obsessive-compulsive disorder (OCD), attention-deficit and hyperactivity disorder (ADHD), autism spectrum disorder (ASD), affective disorders, anxiety disorders, impulse control disorders, and personality disorders (Robertson 2000).…”

Section: Introductionmentioning

confidence: 99%

Oligogenic risk model for Gilles de la Tourette syndrome reveals a genetic continuum of tic disorders

Borczyk

Fichna

Piechota

et al. 2021

Preprint

View full text Add to dashboard Cite

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder from the spectrum of tic disorders (TDs). GTS and other TDs have a substantial genetic component with the heritability estimated at between 60 and 80%. Here we propose an oligogenic risk model of GTS and other TDs using whole-genome sequencing (WGS) data from a group of Polish GTS patients and their families (n=185). The model is based on the overrepresentation of putatively pathogenic coding and non-coding genetic variants in genes selected from a set of 86 genes previously suggested to be associated with GTS. Based on the variant overrepresentation (SKAT test results) between unrelated GTS patients and controls based on gnomAD database allele frequencies five genes (HDC, CHADL, MAOA, NAA11, and PCDH10) were selected for the risk model. Putatively pathogenic variants (n = 98) with the median allele frequency of ~0.04 in and near these genes were used to build an additive classifier which was then validated on the GTS patients and their families. This risk model successfully assigned individuals from 22 families to either healthy or GTS groups (AUC-ROC = 0.6, p < 0.00001). These results were additionally validated using the GTS GWAS data from the Psychiatric Genomic Consortium. To investigate the GTS genetics further we identified 32 genes from the list of 86 genes as candidate genes in 14 multiplex families, including NEGR1 and NRXN with variants overrepresented in multiple families. WGS data allowed the construction of an oligogenic risk model of GTS based on possibly pathogenic variants likely contributing to the risk of GTS and TDs. The model includes putatively deleterious rare and non-coding variants in and near GTS candidate genes that may cooperatively contribute to GTS etiology and provides a novel approach to the analysis of clinical WGS data.

show abstract

Gilles de la Tourette syndrome

Cited by 3 publications

References 67 publications

Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome

Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome

Genomic variants and inferred biological processes in multiplex families with Tourette syndrome

Oligogenic risk model for Gilles de la Tourette syndrome reveals a genetic continuum of tic disorders

Contact Info

Product

Resources

About