Rare missense neuronal cadherin gene (CDH2) variants in specific obsessive-compulsive disorder and Tourette disorder phenotypes
Authors
Moya, Pablo R.Dodman, Nicholas H.
Timpano, Kiara R.
Rubenstein, Liza M.
Rana, Zaker
Fried, Ruby L.
Reichardt, Louis F.
Heiman, Gary A.
Tischfield, Jay A.
King, Robert A.
Galdzicka, Marzena
Ginns, Edward I.
Wendland, Jens R.
UMass Chan Affiliations
Department of PathologyMolecular Diagnostics Laboratory and Clinical Labs
Intellectual and Developmental Disabilities Research Center
Document Type
Journal ArticlePublication Date
2013-08-01Keywords
AdultAntigens, 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
Metadata
Show full item recordAbstract
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.Source
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 siteDOI
10.1038/ejhg.2012.245Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34839PubMed ID
23321619Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/ejhg.2012.245