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.