SHANK3 mutation in consanguineous schizophrenia family in northwest Algeria

Abstract

Introduction

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.

Aims

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.

Methods

This family has received complete clinical (DIGS, DSM-IV criteria), genealogical investigations, CNV analysis using CGH Microarray Kit 244 K (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.

Results

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.

Discussion

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.

Conclusion

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.

Disclosure of interest

The authors have not supplied their declaration of competing interest.