RESEARCH ARTICLE Association of CDH11 With Non-Syndromic ASD An Crepel, 1,2 * Veerle De Wolf, 1,2 Nathalie Brison, 1,2 Berten Ceulemans, 3 Didier Walleghem, 4 Gilian Peuteman, 5,6 Diether Lambrechts, 5,6 Jean Steyaert, 2,7,8 Ilse Noens, 2,9,10 Koen Devriendt, 1,2 and Hilde Peeters 1,2 1 Center for Human Genetics, University Hospitals Leuven, KU Leuven, Leuven, Belgium 2 Leuven Autism Research (LAuRes), Leuven, Belgium 3 Department of Neurology-Pediatric Neurology, Antwerp University Hospital (UZA), University of Antwerp, Edegem, Belgium 4 Antwerp Hospital Network ZNA, University Child and Adolescent Psychiatry, Antwerp, Belgium 5 Vesalius Research Center, VIB, Leuven, Belgium 6 Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium 7 Department of Child and Adolescent Psychiatry, KU Leuven, Leuven, Belgium 8 Department of Clinical Genetics, Academic Hospital Maastricht, and Research Institute Growth & Development (GROW), Maastricht University, Maastricht, the Netherlands 9 Parenting and Special Education Research Unit, University of Leuven, Leuven, Belgium 10 Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts Manuscript Received: 8 November 2013; Manuscript Accepted: 22 April 2014 We report a sporadic patient with Autism Spectrum Disorder (ASD), mild intellectual disability and attention deficit hy- peractivity disorder (ADHD) with a de novo partial deletion of CADHERIN 11 (CDH11). The deletion is associated with one of the breakpoints of a de novo complex chromosomal rearrangement 46,XY,t(3;16;5)(q29;q22;q15)inv4(p14;q21) ins(4;5)(q21;q14.3q15). Cadherins are cell adhesion mole- cules involved in synaptic plasticity. Since genetic evidence points towards a role for cadherins in ASD, we studied the possible contribution of CDH11 to ASD. A case-control association study for 14 SNP variants in 519 ASD cases and 1,192 controls showed significant overrepresentation of rs7187376C/C genotypes in the patient group [P ¼ 0.0049 (Chi-square ¼ 7.90 1 df) and O.R. 3.88 C.I. ¼ 1.403–10.733]. There was no association for C/T versus T/T [P ¼ 0.6772 (Chi- square ¼ 0.17 1 df)] nor was there association at the allelic level [P ¼ 0.4373 (Chi-square ¼ 0.6 1 df)]. In addition to the association of common variants in CDH11 with ASD, we studied the possible contribution of rare variants by sequenc- ing CDH11 in 247 patients, and found three novel variants in the coding region of CDH1, of which two variants were unlikely to be causal. Targeted CNV screening in these 247 patients did not reveal copy number variation in CDH11. In conclusion, the data provide evidence for the involvement of CDH11 in ASD which is consistent with the association of other cadherins with ASD and neuropsychiatric diseases. Ó 2014 Wiley Periodicals, Inc. Key words: cadherin; autism; chromosomal rearrangement; de novo INTRODUCTION Autism Spectrum Disorders (ASDs) are a group of neurodevelop- mental disorders characterized by a triad of deficits: social interac- tion, communication skills and language development, and stereotypic and repetitive behaviors. ASD has a strong genetic component, with an estimated heritability of 70–90% [Bailey et al., 1995; Schaaf and Zoghbi, 2011]. Nevertheless, the genetic How to Cite this Article: Crepel A, De Wolf V, Brison N, Ceulemans B, Walleghem D, Peuteman G, Lambrechts D, Steyaert J, Noens I, Devriendt K, Peeters H. 2014. Association of CDH11 with non- syndromic ASD. Am J Med Genet Part B 9999:1–8. Conflict of interest: none. Grant sponsor: Research Actions KULeuven GOA/12/015; Grant sponsor: Belgian Science Policy Office Interuniversity Attraction Poles (BELSPO-IAP) IAP; Grant number: P7/43-BeMGI. K.D.; Grant sponsor: Clinical Research Foundation of UZLeuven.  Correspondence to: Hilde Peeters, Center for Human Genetics, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: hilde.peeters@med.kuleuven.be Article first published online in Wiley Online Library (wileyonlinelibrary.com): 00 Month 2014 DOI 10.1002/ajmg.b.32243 Ó 2014 Wiley Periodicals, Inc. 1 Neuropsychiatric Genetics