Progress in research on molecular mechanism of facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD), characterized by symmetric or asymmetric muscular weakness of the initial onset of facial, shoulder-girdle and upper arm muscles, and descending to limb muscles, is a classical autosomal dominant myopathy with high clinical diversity and relatively good prognosis. FSHD is catigorized into two types, FSHD1 and FSDH2. Previous studies have demonstrated that 95% patients with FSHD1 were associated with a contraction of D4Z4 microsatellite repeats on chromosome 4q35, which was pathogenic in the genetic backgrounds, including a special sequence of simple sequence length polymorphism (SSLP) proximal to the D4Z4 repeats and the 4qA/4qB polymorphism distal to the repeats. In recent years, several reports have confirmed that 4q35 locus leads to DNA hypomethylation and inner DUX4 gene transcription by epigenetic effect. The abnormal expression of DUX4 further activates several genes, which inhibit myogenesis, sensitize cells to oxidative stress and induce muscle atrophy. And not only that, FSHD2 is formed by another methylation regulation gene—— SMCHD1 mutations. More and more evidences supported that toxic gain of function mechanism plays an important role in the occurrence of FSHD. The DUX4 gene becomes an important target for treatment study in the future. DOI: 10.3969/j.issn.1672-6731.2017.08.004