Chimeric fusion gene transcripts ETV6-RTN1 and RTN1-ETV6. (A) In silico prediction of amino acid sequences encoded by fusion transcripts. ETV6-RTN1 fusion transcript, originating from exon 1 of ETV6 and part of exon 2 of RTN1, houses a frameshift downstream of the fusion point, resulting in a premature stop codon. The transcript is predicted to encode 86 amino acids. RTN1-ETV6 fusion transcript, originating from exon 1 of RTN1 and exons 2, 3, and part of 4 of ETV6, also houses a frameshift downstream of the fusion point resulting in a premature stop codon. This transcript is predicted to encode 178 amino acids. Electropherograms of novel exon–exon junctions, resulting from the translocation, support the in silico–predicted sequences of fusion transcripts. (B) Gel images (2% agarose gel) supporting the expression of both fusion transcripts in remission and leukemia from the 2 affected female subjects (III:3 and IV:2) and germline of an unaffected carrier (III:2). Positive control ribosomal RNA 18S5N is shown in the bottom gel image. 100bp Plus DNA Ladder from GeneRuler (Thermo Fisher Scientific). (C) Two-dimensional models of ETV6 and RTN1 protein with approximate locations of breakpoints indicated by red bars. Functional domains are not retained in theoretical fusion proteins. Breakpoints are located upstream of functional domains, and all sequence downstream of breakpoints is subject to frameshift introducing premature stop codons, consequently disrupting encoded functional domains.