Tourette’s Syndrome: Genetic Basis

Author: Will Bowman

Overview of exome sequencing as a technique.


A variety of studies have focused on the genetic basis for inheritance of Tourette’s Syndrome. Most studies are of European descent, but studies of Asian populations have also been performed. In many cases however, the genetic causes between these two populations is distinct and uninformative to the other.

Via exome sequencing of sporadic affected patients from nine families, 30 de novo mutations were identified among which a missense mutation in rapamycin coding gene (RICTOR) was found. This mutation is predicted to be hazardous, however it is also rare. RICTOR is thought to be implicated in the development of sporadic Tourette’s Syndrome (Eriguchi, Y. et al. 2017).

Genome wide study on 2434 TS cases in European populations found 2 significant gene loci. NRXN1, a neurexin coding gene which have roles in synaptic function and formation, and CNTN6, a member of the immunoglobulin superfamily which plays a role in formation of axon connections. Deletions in NRXN1 and duplications in CNTN6 are thought to be rare but significant mutations to the formation of Tourette’s Syndrome (Huang, A. et al. 2017).

Exome sequencing of 325 TS trios has located 4 major genes associated with TS. WWC1, a cytoplasmic phosphoprotein that is a probable regulator of Hippo/SWH signaling pathway that is involved in restricting proliferation and promoting apoptosis and is associated with memory, CELSR3, a membrane receptor protein that is associated with cell/cell signalling during nervous system formation, NIPBL, a cohesin loading factor that promotes neuron migration during brain development via regulation of other related genes, and FN1, which encodes fibronectin which is a glycoprotein which helps bind to cell surfaces and plays a role in maintenance of cell adhesion and cell shape (Willsey, A. et al. 2017).

Rare mutations in HDC gene is found in two generation pedigree of a family with high frequency of TS. In European populations, these mutations are linked to high incidence of TS, but not in Chinese populations. HDC is rate limiting enzyme in histamine biosynthesis, and is linked to signalling pathways involving neurotransmitters (Dong, H. et al. 2016).

In future work, genetic studies need to use larger sample sizes, the lack of which led several of these studies to suffer. Furthermore, many of these genes are isolated to either an Asian or European population, therefore many of the connections made are not of relevance to more common forms of Tourette’s Syndrome, but represent rare ethnically linked cases.




Dong, He, Wenmiao Liu, Meixin Liu, Longqiang Xu, Qiang Li, Ru Zhang, Xin Zhang, and Shiguo Liu. 2016. “Investigation of a Possible Role for the Histidine Decarboxylase Gene in Tourette Syndrome in the Chinese Han Population: A Family-Based Study.” PloS One 11 (8): e0160265.


Eriguchi, Yosuke, Hitoshi Kuwabara, Aya Inai, Yuki Kawakubo, Fumichika Nishimura, Chihiro Kakiuchi, Mamoru Tochigi, et al. 2017. “Identification of Candidate Genes Involved in the Etiology of Sporadic Tourette Syndrome by Exome Sequencing.” American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics 174 (7): 712–23.


Huang, Alden Y., Dongmei Yu, Lea K. Davis, Jae Hoon Sul, Fotis Tsetsos, Vasily Ramensky, Ivette Zelaya, et al. 2017. “Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.” Neuron 94 (6): 1101–1111.e7.


Willsey, A. Jeremy, Thomas V. Fernandez, Dongmei Yu, Robert A. King, Andrea Dietrich, Jinchuan Xing, Stephan J. Sanders, et al. 2017. “De Novo Coding Variants Are Strongly Associated with Tourette Disorder.” Neuron 94 (3): 486–499.e9.


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