Translocation t(12;14)(p13.2;q23.1). (A) Karyotype images and models of chromosome pairs 12 and 14. The derivate chromosomes, der(12)t(12;14)(p13.2;q23.1)c and der(14)t(12;14)(p13.2;q23.1)c, created by the translocation t(12;14)(p13.2;q23.1), are indicated by # and *. (B) Model of genetic events at breakpoints and fusions. ETV6 and RTN1 are transcribed from the positive strand and negative strand, respectively. ETV6 intron 1 (positive strand) has fused to RTN1 intron 1 (negative strand) creating the chimeric fusion gene ETV6-RTN1 (indicated in red). RTN1 intron 1 (negative strand) has fused to ETV6 intron 1 (positive strand) creating the chimeric fusion gene RTN1-ETV6 (indicated in blue). An 8 bp deletion in ETV6 and a 2 bp deletion in RTN1 have occurred at the breakpoints before fusion. Microhomologies, CA and AAC, were found at the fusion points of each derivate chromosome. A 7 bp insertion was found upstream of the fusion in ETV6 intron 1. (C) Sanger traces of genomic sequence from ETV6-RTN1 and RTN1-ETV6 chimeric fusion genes, supporting identical breakpoints in affected female subjects (III:3 and IV:2) and unaffected carrier (III:2). (D) Germline and remission WGS data from affected female subjects (III:3 and IV:2) and unaffected carrier (III:2) visualized in IGV^40,60  showing paired-end reads at translocation breakpoint sites on chromosomes 12 and 14. Coloring of reads (chr12 orange and chr14 purple) indicate that the 2 mates in a read-pair are mapping to different chromosomes, in this case chromosome 12 (ETV6 intron 1) and chromosome 14 (RTN1 intron 1). Multi-coloring of reads indicates mismatched nucleotides. Read-pairs mapping to 2 different chromosomes and mismatched bases on either side of the breakpoint support the presence of translocation breakpoints at either position. Gray arrows indicate the chromosomal regions where breakpoints are found. The genomic positions of breakpoints and sequences at fusion sites are identical in all 3 individuals analyzed.