Table 2.

Summary of human genetic studies assessing associations between Slitrks and neuropsychiatric disorders OCD-spectrum disorders

Slitrk gene	Disorder	Main conclusions of the studies		Refs
Slitrk1	GTS	•	Identified 3 patients (out of 174 unrelated individuals with GTS) carrying mutations in the Slitrk1 gene in 174; one patient had the varCDfs variant, while the other two expressed var321. These mutations were absent in more than 3600 control subjects.	[27]
		•	No mutations found in 6 patients belonging to a large Dutch family with GTS	[62]
		•	No association of varCDfs or var321 was reported in a cohort of 812 GTS patients from a Costa Rican and AJ population, however, over- representation of var321 in AJ population was found.	[60]
		•	Five subjects with GTS were identified in the AJ population who contained the var321, two of these did not transmit the mutation to affected child. One individual was found with var321 but did not have GTS.
		•
		•	var321 nor varCDfs were found in 82 Caucasian patients with GTS; a new mutation was found that neither changed amino acid nor altered mRNA splicing.	[58]
		•
		•	Did not find var321 nor varCDfs in 208 affected children, however, found significant association with 3 other novel SNPs in the Slitrk1 gene	[64]
		•
		•	No var321 or varCDfs found in 92 Austrian patients with GTS. A new 3’UTR variant was found in one patient and parents with GTS and was absent in 192 control individuals.	[66]
	GTS, CT	•	Large sequencing study did not find association between Slitrk1 and GTS or CT. Out of 1048 individuals with GTS or CT one individual carried var321; a second carrier of var321 had OCD. Neither transmitted the mutation to GTS offspring. Both of these carriers were of AJ descent.	[61]
	GTS, CT, OCD	•	Provided additional information regarding the ethnicity of the two initially identified variants that are of European descent and found 4 additional affected individuals carrying var321 of Spanish, Eastern Europe and Caucasian. In addition, one AJ unaffected individual with var321 was identified.	[63]
	OCD	•	Did not find var321 nor varCDfs in 322 subjects with OCD	[59]
	TTM	•	Two novel non-synonymous mutations were found in a cohort of 44 patients with TTM and which were absent in 3000 healthy controls. var321 and varCDfs were not found in this population.	[53]
Slitrk2	SCZ	•	Systematic re-sequencing of X-chromosome genes found two novel missense variants in Slitrk2 gene in patients with SCZ and in their affected siblings	[97]

Abbreviations: CT, chronic tics; AJ, Ashkenazi Jew; SCZ, Schizophrenia;