A few examples follow: large structural changes affecting MMR genes can be missed by conventional (Sanger or short-read next-generation) sequencing, such as the Finnish MLH1 founder variant, a 3.5 kb deletion of exon 16 and flanking intronic sequence [85,92], or an inversion of MSH2 exons 2–6 discovered in Australian LS patients [93]. Here, MSH2 is linked to Leigh syndrome.