Abstract
Facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant neuromuscular disorder, has been causally related to deletion of tandemly arrayed 3.3 kb repeats (D4Z4) on chromosome 4q35. Although increased expression of several 4q35 genes has been reported, two recent studies dispute this, finding no significant changes in the transcriptional level of any of the 4q35 genes, among which is the heart and muscle-specific isoform of the adenine nucleotide translocator (ANT1). We found markedly increased levels of ANT1 protein in both unaffected and affected FSHD muscles in comparison to control healthy muscles. Comparative protein expression analysis between healthy, Duchenne muscular dystrophy, and FSHD muscle shows that proteins involved in mitochondrial function and protection from oxidative stress are also reproducibly and specifically modified in all FSHD muscles, including clinically unaffected muscles. Increased ANT1 expression and mitochondrial dysfunction may thus be initial events in FSHD pathogenesis and represent potential therapeutic targets.