Targeted gene under study:

 CSMD2 (OMIM * 608398) 


Common variants in the CSMD1-3 paralogs were shown to be GWAS-associated with 
neurodevelopmental and psychiatric disorders. These CUB and Sushi domains-containing 
synaptic proteins play a role in neuron development. 
GnomAD suggests that CSMD2 is under constraint and that missense variation with Z
score=5.45 could be deleterious. Consistent with this hypothesis, we identified fifteen 
individuals carrying biallelic missense mutations in CSMD2 in developmental 
delay/intellectual disability cohorts. Patients also present with autism, attention deficit 
hyperactivity disorder, brain anomalies and epilepsy. While the identified mutations are 
spread along the gene, 3D in silico modelling of the encoded proteins shows that the 
mutated residues are structurally close. 
Zebrafish ablated using crispr-cas for the orthologous csmd2 presented with microcephaly, a 
smaller cerebellum, a decrease in the number of connections between their optic tecta a 
higher number of abnormal peripheral neuronal branches and a decreased velocity further 
substantiating a possible role of this gene in neurogenesis and synapse formation. 

Coordinating clinicians

Alexandre Reymond –
Clara Pailler-Pradeau – 


Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland

Specific requirements beyond clinical data and genotype data sharing:

1- Re-analysis of DNA samples: Yes

2- Resampling of patients: No

3- Linked to a translational/basic research project: Yes