Molecular diagnosis of facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited neuromuscular disorder after Duchenne muscular dystrophy and myotonic dystrophy. The gene underlying FSHD was mapped to chromosome 4q35 in 1990 and was shown to be closely linked to locus D4F104S1. Although D4F104S1-associated deletions are closely associated with FSHD, the identity and location of the FSHD gene (or genes) still remain elusive, as does the mechanistic basis of the disease. In addition, although approximately 5% of FSHD families fail to exhibit linkage to 4q35, a putative second locus remains unidentified. The search for the FSHD gene has been hampered both by sequence homologies between the 4q35 candidate region and other chromosomal regions and by the presence of many highly repetitive sequences. Molecular diagnosis for FSHD is usually offered with 98% accuracy but because of its complexity, a much more simple test would be preferable. Indeed, the identification of the FSHD gene itself should potentiate major improvements in diagnostic testing.