Cntnap2 is disrupted in a family with gilles de la tourette syndrome and obsessive compulsive disorder

Verkerk, Annemieke J.M.H.; Mathews, Carol A.; Joosse, Marijke; Eussen, Bert; Heutink, Peter; Oostra, Ben A.

doi:10.1016/s0888-7543(03)00097-1

Cited by 221 publications

(161 citation statements)

References 34 publications

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…36,38 So far it has been suggested as a candidate gene for various neuropsychiatric disorders, [39][40][41][42][43][44][45] however little is known about its specific function and regulation. This protein contains multiple interaction domains such as laminin G, fibrinogen-like domains and epidermal growth factor (EGF)-repeat domains that are also found in members of the fibrillins and fibulins protein families.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

et al. 2010

View full text Add to dashboard Cite

Genetic and nongenetic factors contribute to development of pseudoexfoliation (PEX) syndrome, a complex, age-related, generalized matrix process frequently associated with glaucoma. To identify specific genetic variants underlying its etiology, we performed a genome-wide association study (GWAS) using a DNA-pooling approach. Therefore, equimolar amounts of DNA samples of 80 subjects with PEX syndrome, 80 with PEX glaucoma (PEXG) and 80 controls were combined into separate pools and hybridized to 500K SNP arrays (Affymetrix). Array probe intensity data were analyzed and visualized with expressly developed software tools GPFrontend and GPGraphics in combination with GenePool software. For replication, independent German cohorts of 610 unrelated patients with PEX/PEXG and 364 controls as well as Italian cohorts of 249 patients and 190 controls were used. Of 19, 17 SNPs showing significant allele frequency difference in DNA pools were confirmed by individual genotyping. Further single genotyping at CNTNAP2 locus revealed association between PEX/PEXG for two SNPs, which was confirmed in an independent German but not the Italian cohort. Both SNPs remained significant in the combined German cohorts even after Bonferroni correction (rs2107856: P c ¼0.0108, rs2141388: P c ¼0.0072). CNTNAP2 was found to be ubiquitously expressed in all human ocular tissues, particularly in retina, and localized to cell membranes of epithelial, endothelial, smooth muscle, glial and neuronal cells. Confirming efficiency of GWAS with DNA-pooling approach by detection of the known LOXL1 locus, our study data show evidence for association of CNTNAP2 with PEX syndrome and PEXG in German patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

et al. 2010

View full text Add to dashboard Cite

show abstract

“…2 This chromosomal translocation likely disrupted the normal expression of genes located elsewhere in the genome. Since then, other patients have been identified with chromosomal rearrangements affecting multiple genes including CNTNAP2, which are likely to confound the effects resulting from CNTNAP2 mutation [3][4][5][6][7][8][9] (Table 1).…”

Section: Cntnap2 and Cognitive Disorders Mutations Of Cntnap2mentioning

confidence: 99%

Shining a light on CNTNAP2: complex functions to complex disorders

2013

View full text Add to dashboard Cite

The genetic basis of complex neurological disorders involving language are poorly understood, partly due to the multiple additive genetic risk factors that are thought to be responsible. Furthermore, these conditions are often syndromic in that they have a range of endophenotypes that may be associated with the disorder and that may be present in different combinations in patients. However, the emergence of individual genes implicated across multiple disorders has suggested that they might share similar underlying genetic mechanisms. The CNTNAP2 gene is an excellent example of this, as it has recently been implicated in a broad range of phenotypes including autism spectrum disorder (ASD), schizophrenia, intellectual disability, dyslexia and language impairment. This review considers the evidence implicating CNTNAP2 in these conditions, the genetic risk factors and mutations that have been identified in patient and population studies and how these relate to patient phenotypes. The role of CNTNAP2 is examined in the context of larger neurogenetic networks during development and disorder, given what is known regarding the regulation and function of this gene. Understanding the role of CNTNAP2 in diverse neurological disorders will further our understanding of how combinations of individual genetic risk factors can contribute to complex conditions.

show abstract

“…4 Mutations in CNTNAP2 have been associated with two distinct neurological disorders: cortical dysplasia-focal epilepsy syndrome (CDFE, OMIM 610042) 5 and Gilles de la Tourette syndrome (GTS, OMIM 137580). 6 CDFE is characterized by cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes.…”

Section: Introductionmentioning

confidence: 99%

Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome

et al. 2007

View full text Add to dashboard Cite

Caspr2 is a member of neurexin superfamily, members of which are transmembrane proteins that mediate cellular interactions in the nervous system. Recently, truncation of the CNTNAP2 gene coding for the Caspr2 protein has been suggested to be associated with the Gilles de la Tourette syndrome, a neurological disorder characterized by motor and vocal tics, and behavioral anomalies. In this study, we describe a familial balanced reciprocal translocation t(7;15)(q35;q26.1) in phenotypically normal individuals. The 7q35 breakpoint disrupts the CNTNAP2 gene, indicating that truncation of this gene does not necessarily lead to the symptoms of the complex Gilles de la Tourette syndrome.

show abstract

Cntnap2 is disrupted in a family with gilles de la tourette syndrome and obsessive compulsive disorder

Cited by 221 publications

References 34 publications

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

Shining a light on CNTNAP2: complex functions to complex disorders

Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome

Contact Info

Product

Resources

About