Oligonucleotide-Based Therapy for FTD/ALS Caused by the C9orf72 Repeat Expansion: A Perspective

Figure 1

Structure of the C9orf72 locus and its three primary transcripts. Two alternative first exons are used, 1a and 1b, and both of these lie upstream of the translation start site. Between exons 1a and 1b lies the hexanucleotide expansion region. Note that two putative CpG islands lie either side of the expansion. The shorter of these regions, CpG 20, overlaps with much of the sequence of exon 1a. Although there are three transcripts, the position of the ATG start codon in exon 2 means that only two protein isoforms are translated: isoform A is 481 amino acids long, while the shorter isoform B is only 222 amino acids in length.