[Progress in researches on the molecular genetics of facioscapulohumeral muscular dystrophy]

Facioscapulohumeral muscular dystrophy(FSHD) is an autosomal dominant neuromuscular disorder characterized by progressive weakness of the facial, shoulder and upper arm muscles. The major gene involved has been mapped to chromosome 4q35. There is the evidence for genetic heterogeneity. The FSHD- associated DNA rearrangements are due to deletions of integral copies of the 3.3 kb tandem repeated unit from the subtelomeric region on chromosome 4q35. A valuable molecular diagnostic test for FSHD has been created with the use of p13E-11 probe to detect the EcoR I/Bln I double digestion fragment which is usually smaller in FSHD patient than in normal indivdual. Since the FSHD gene has not been identified yet, the exact molecular pathogenesis of FSHD remains unclear. The hypothesis of position effect variegation has been postulated as the underlying genetic mechanism of FSHD. FRG1 (FSHD region gene 1) from human chromosome 4q35 is identified as a candidate gene for FSHD. A significant correlation between the size of rearrangements associated with FSHD and the clinical phenotype has been found. The various rearrangement fragment size may explain the wide range of clinical severity in FSHD.