Figures & data
Figure 1. Possible mechanisms in FSHD. By itself, DUX4 expression from a contracted allele might not be sufficient to cause FSHD symptoms (A). Short telomeres would increase expression, but still might not be sufficient (B). A variety of additional factors could cooperate with DUX4 to increase muscle toxicity and produce weakness. A far from exhaustive list could include compound heterozygosity (having two contracted alleles, each increasing the dose of DUX4 expression so the total was sufficient to exceed a threshold, (C), and other conditions that compromised muscle function (such as a subclinical myopathy (D, E), or the increased expression of other factors that by themselves produced decreased muscle reserve but not overt symptoms: (F-H). Telomere length could modulate the age of onset and severity of symptoms by influencing DUX4 levels or the level of other genes.
