Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes

UMMS Affiliation

Intellectual and Developmental Disabilities Research Center; Molecular Diagnostics Laboratory and Clinical Labs; Department of Pathology

Publication Date


Document Type



Adult; Antigens, CD; Blotting, Western; Cadherins; DNA Mutational Analysis; Genotype; HEK293 Cells; Humans; *Mutation, Missense; Obsessive-Compulsive Disorder; Phenotype; Psychiatric Status Rating Scales; Tourette Syndrome; Transfection


Genetics | Mental Disorders | Molecular Genetics | Psychiatric and Mental Health | Psychiatry and Psychology


The recent finding that the neuronal cadherin gene CDH2 confers a highly significant risk for canine compulsive disorder led us to investigate whether missense variants within the human ortholog CDH2 are associated with altered susceptibility to obsessive-compulsive disorder (OCD), Tourette disorder (TD) and related disorders. Exon resequencing of CDH2 in 320 individuals identified four non-synonymous single-nucleotide variants, which were subsequently genotyped in OCD probands, Tourette disorder probands and relatives, and healthy controls (total N=1161). None of the four variants was significantly associated with either OCD or TD. One variant, N706S, was found only in the OCD/TD groups, but not in controls. By examining clinical data, we found there were significant TD-related phenotype differences between those OCD probands with and without the N845S variant with regard to the co-occurrence of TD (Fisher's exact test P=0.014, OR=6.03). Both N706S and N845S variants conferred reduced CDH2 protein expression in transfected cells. Although our data provide no overall support for association of CDH2 rare variants in these disorders considered as single entities, the clinical features and severity of probands carrying the uncommon non-synonymous variants suggest that CDH2, along with other cadherin and cell adhesion genes, is an interesting gene to pursue as a plausible contributor to OCD, TD and related disorders with repetitive behaviors, including autism spectrum disorders.

DOI of Published Version



Moya PR, Dodman NH, Timpano KR, Rubenstein LM, Rana Z, Fried RL, Reichardt LF, Heiman GA, Tischfield JA, King RA, Galdzicka M, Ginns EI, Wendland JR. Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes. Eur J Hum Genet. 2013 Aug;21(8):850-4. doi: 10.1038/ejhg.2012.245. Epub 2013 Jan 16. PubMed PMID: 23321619; PubMed Central PMCID: PMC3722668. Link to article on publisher's site

Journal/Book/Conference Title

European journal of human genetics : EJHG

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PubMed ID