Association of CDH11 with non‐syndromic ASD

Abstract

We report a sporadic patient with Autism Spectrum Disorder (ASD), mild intellectual disability and attention deficit hyperactivity 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 molecules 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 (Chisquare 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 sequencing 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.

A Subset of Autism-Associated Genes Regulate the Structural Stability of Neurons

“…CDH8. CDH9, CDH10, CDH11 , and CDH13 (Wang et al, 2010; Chapman et al, 2011; Hussman et al, 2011; Pagnamenta et al, 2011; Sanders et al, 2011; O’Roak et al, 2012b; Prandini et al, 2012; Connolly et al, 2013; Walker and Scherer, 2013; Crepel et al, 2014; Krumm et al, 2015); non-clustered protocadherins: PCDH9, PCDH10 , and PCDH19 (Morrow et al, 2008; Depienne et al, 2009; Camacho et al, 2012; O’Roak et al, 2012b; Prasad et al, 2012; Girirajan et al, 2013; van Harssel et al, 2013) ; and an atypical cadherin, FAT1 (Hussman et al, 2011; Neale et al, 2012; Cukier et al, 2014; Kenny et al, 2014). In general, the extracellular domain of cadherins contains five cadherin repeats/EC motifs that mediate Ca 2+ -dependent homophilic adhesion (Tanihara et al, 1994).…”

Behavioral phenotypes of genetic mouse models of autism

“…In contrast to disorders such as Huntington's disease and Fragile X syndrome, there is no one specific gene responsible for all cases of autism. Rather, a growing number of de novo single gene mutations and CNVs have been identified in people with autism (Alarcon et al ; Bucan et al ; Butler et al ; Buxbaum et al ; Cook & Scherer ; Crepel et al ; Glessner et al ; Iossifov et al ; Krumm et al ; Kumar et al ; Lawson‐Yuen et al ; Leblond et al ; Michaelson et al ; Morrow ; Neale et al ; O'Roak et al ; Pinto et al ; Szatmari et al ; Vernes et al ; Wang et al ; Yuen et al ). Mutations in common gene variants and de novo coding mutations may be responsible for up to 50% of ASD cases (Gaugler et al ; Iossifov et al ; Miles ).…”

Identification of CDH11 as an ASD Risk Gene by Matched-gene Co-expression Analysis and Mouse Behavioral Studies

“…Some cadherin genes were not signi cantly co-expressed with hcASDs under any of the matched conditions; these genes were referred to as tetra-negative genes (TetraN; Additional le 10: Table S9). Several recent genetic studies have implicated two type II cadherins, CDH11 and CDH9, in ASD and other psychiatric diseases [42][43][44][45][46]. As CDH11 and CDH9 belonged to the TetraM and TetraN gene sets, respectively, we hypothesized that CDH11, but not CDH9, is more likely to be an authentic ASD risk gene.…”