Exchange of subtelomeric regions between chromosomes 4q and 10q: a novel way to revert the FSHD genotype.

The most common form of facioscapulohumeral dystrophy (FSHD1) is caused by a partial loss of the D4Z4 macrosatellite repeat array in the subtelomeric region of the chromosome 4q. FSHD1 patients typically carry 1–10 D4Z4 repeats, whereas non-affected individuals have 11–150 repeats. The ~150 kb subtelomeric region of the chromosome 10q exhibits an almost complete sequence identity (~99%) to the 4q, including the D4Z4 array, nevertheless contractions of the repeat array on chromosome 10 do not cause FSHD or any known disease, with rare exceptions. This way we replaced the pathological 4q35 locus with the non-pathological 10q26, which led to the reconstitution of the normal expression pattern of DUX4 target genes and myoblast differentiation capacity.