Several studies have asserted the existence of a strong and complex genetic component in the determination of psychotic disorders. GWAS studies conducted over the past decade lead to the identification of only a few low effect associations, calling questioning the hypothesis of “common disease – common variants” for a model involving a large number of rare variants.

Here, we studied a multigenerational multiplex family with schizophrenia a high rate of consanguinity, located in the northwest of Algeria. This study aims to identify inherited rare variants of schizophrenia using new genetic technologies.

This family has received complete clinical (DIGS, DSM-IV criteria), genealogical investigations, CNV analysis using CGH Microarray Kit 244K (Santa Clara, CA) and WES (by GAIIx Illumina/HiSeq 2000) focused in CNV regions, that were performed in the department of genetics in the university hospital of Geneva.

We identify 11 affected members by psychotic disorders. The main CNVs analysis results found in a schizophrenic member a Del 22q13.33 affecting SHANK3 gene. WES regarding these regions identified a mutation at position 511178000 in SHANK3 gene in all the selected affected relatives.

Several studies have asserted the association of SHANK3 mutations with schizophrenia and autism disorders. This is the first observation of rs511,178,000 in schizophrenia phenotype.

In total, this highly informative family have identified new rare genetic variant of schizophrenia. The search for this mutation in wider control population in would be useful to validate these data.