Facioscapulohumeral muscular dystrophy: new insights from compound heterozygotes and implication for prenatal genetic counselling

Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary muscle disease affecting approximately 1 in 20,000 individuals.  The genetic defect associated with FSHD does not reside in any protein-coding gene.  Instead, FSHD had previously been correlated with a specific set of DNA variations (termed haplotype) at 4q35. Using genetic and clinical information from the Italian National Registry for FSHD, we found that 52% of subjects carrying the disease-associated haplotype are healthy, demonstrating that this haplotype alone is insufficient for disease. In addition, we observed a high number of patients carrying two copies of this haplotype, suggesting a population frequency of 1.2% for this haplotype. Therefore, this set of genetic markers is far more prevalent than FSHD disease, supporting our hypothesis that additional factors are required for disease. Our findings undermine the current paradigms of genetic counseling and prenatal diagnosis for the disease. (By Prof. Rossella Tupler, http://jmg.bmj.com/content/early/2012/01/03/jmedgenet-2011-100454.abstract?papetoc )