Pedigree segregation and somatic analysis
By Sanger sequencing, we detected the c.636+3_636+6del variant at the heterozygous state in one apparently healthy paternal uncle as well as in the cousin with schizophrenia (III-18). In this latter, the variant was inherited from the apparently unaffected father and was also present in the younger healthy brother (Figure 1a). WES analysis in III-18 excluded the presence of additional pathogenic variants in known schizophrenia-associated genes (Table S1) as well as copy number variations (CNVs). DNA from other family members was not available for the analysis. Considering the crucial role of TDP2 in NHEJ and maintenance of genome stability and the development of a colorectal cancer in the patients’ mother, we were prompted to examine whether a second somatic hit in TDP2 may have occurred. However, any pathogenic coding variant was detected in the DNA obtained from the tumour sample.