title: Pathogenetic model for Tourette syndrome delineates overlap with related neurodevelopmental disorders including Autism.
abstract: Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder characterised by motor and vocal tics. Despite decades of research, the aetiology of TS has remained elusive. Recent successes in gene discovery backed by rapidly advancing genomic technologies have given us new insights into the genetic basis of the disorder, but the growing collection of rare and disparate findings have added confusion and complexity to the attempts to translate these findings into neurobiological mechanisms resulting in symptom genesis. In this review, we explore a previously unrecognised genetic link between TS and a competing series of trans-synaptic complexes (neurexins (NRXNs), neuroligins (NLGNs), leucine-rich repeat transmembrane proteins (LRRTMs), leucine rich repeat neuronals (LRRNs) and cerebellin precursor 2 (CBLN2)) that links it with autism spectrum disorder through neurodevelopmental pathways. The emergent neuropathogenetic model integrates all five genes so far found to be uniquely disrupted in TS into a single pathogenetic chain of events described in context with clinical and research implications.
authors.affiliation: Department of Human Genetics, Ingham Institute, School of Medicine, University of Western Sydney, Sydney, NSW, Australia.
authors.forename: R A
authors.initials: RA
authors.lastname: Clarke
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: V
authors.initials: V
authors.lastname: Eapen
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D010450:Endopeptidases / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008954:Models, Biological; D008960:Models, Psychological; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D005879:Tourette Syndrome / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D051178:alpha Catenin / Q000235:genetics*
chemical_list: C403049:CNTNAP2 protein, human; C495273:CTNNA1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015816:Cell Adhesion Molecules, Neuronal; D008565:Membrane Proteins; C430845:NLGN4X protein, human; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D051178:alpha Catenin; D010450:Endopeptidases; C425070:IMMP2L protein, human