Analysis of the translocation events between the repeat arrays from chromosomes 4q35 and 10q26 in the South Africa facioscapulohumeral muscular dystrophy (FSHD) population

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive autosomal dominant myopathy, preferentially affecting facial, shoulder girdle and upper-arm muscles. It is one of the most common muscular dystrophies with a prevalence of 1 in 20,000. The rearrangement that results in FSHD entails a deletion of an integral number of 3.3 kb repeat arrays on chromosome 4q35. A candidate gene for this disorder has, however, yet to be identified. Data suggests a position effect variegation model resulting in FSHD. Southern blot analysis has led to the identification of an additional locus with 95% homology to 4q35, which was subsequently mapped to chromosome 1 0q26. This region also undergoes a deletion of 3.3 kb repeat arrays in a similar fashion to 4q35. A deletion fragment located on chromosome 1 0q is, however, non-pathogenic and does not result in FSHD, but rather compromises accurate molecular diagnoses. Previous data suggested a model for subtelomeric plasticity due to the occurrence of DNA translocations between the 4-type and 10-type arrays. The high degree of homology between these fragments may be the predisposing factor that has led to these translocations being observed in 20% of the Dutch population. The objectives of this study were to optimise the Bg/ 11 - Bin I dosage test via a nonradioactive protocol and to verify the presence of translocation events between the 4q and 1 0q arrays in 80 to 100 individuals selected from South African FSHD families. Results obtained from this study suggest a lower translocation frequency in the South African FSHD population when compared to previously reported frequencies. However, the small sample size implies that inferring statistical significance would be unrealistic. The turnaround time for molecular FSHD diagnosis has been reduced significantly via the standardisation of this non-radioactive detection protocol.