Facioscapulohumeral muscular dystrophy (FSHD)

Facioscapulohumeral muscular dystrophy is associated with the deletion 3.3 kb units of a tandem repeat on chromosome 4q. This muscular dystrophy is recognised as the third most frequent muscular dystrophy and affects mainly muscles of the face, shoulder, upper arm and legs.

This disorder has a late-onset and most affected individuals are affected by the second decade of life. FSHD is clinically extremely heterogeneous which complicates its diagnosis via clinical symptoms alone. FSHD is the first disorder described to display position effect variegation in the human genome.

The current research programme in FSHD aims to characterise the South African FSHD population on a molecular level, for the first time.

The South African FSHD pedigrees are unique in the world, with some spanning across more than five generations. Haplotype analyses of the South African population indicate linkage of the FSHD phenotype to the locus on chromosome 4q.

Currently the size of deletion fragments in the South African FSHD population is investigated via Southern blot analysis.

Unique contributions from this research project are summarised below:

  • First analysis of the South African FSHD population on a molecular level.
  • Evidence of a dual founder effect in the South African FSHD population.
  • Evidence that recombination events between the traditional FSHD haplotype, generated via STR analysis, and the FSHD locus exists in the South African population.
  • Diagnosis and confirmation of clinical FSHD diagnoses, on the molecular level.
  • Establishment of FSHD clinics at the Faculty of Medicine, University of Pretoria.
  • The age of the FSHD deletion event was dated via investigation of ancestral DNA samples from an indigenous South African population.

Future objectives of this project include estimation of the translocation frequency between homologous repeat elements on chromosomes 4q and 10q and the length of the deletion fragment that is pathogenic in the South African population. A list of collaborators on this multi-disciplinary project is indicated below.

Current and previous collaborators were from the following institutions:

  • Dept. of Human Genetics, Leiden University, the Netherlands.
  • Centre for Molecular and Mitochondrial Medicine and Genetics, University of California at Irvine, CA, USA.
  • Genome Therapeutics Corporation, Boston, MA, U.S.A.
  • Dept. of Neurology, University of Pretoria, South Africa.