No evidence of genetic heterogeneity in Brazilian facioscapulohumeral muscular dystrophy families (FSHD) with 4q markers.

The gene responsible for facioscapulohumeral muscular dystrophy (FSHD), an autosomal dominant neuromuscular condition, has been mapped to chromosome 4. Until recently, the two closest available markers were D4S139 and D4S163 but a new marker (p13E-11) which recognizes de novo rearrangements in isolated cases of FSHD characterized by shorter EcoRI fragments has been now identified. Linkage analysis in FSHD families with p13E-11 shows that usually a smaller fragment segregates with the disease gene among the affected individuals from each genealogy. In the present paper, we report the results from linkage analysis with the marker loci D4S163 and D4S139 in 6 FSHD families and with p13E-11 in these and in 6 other additional Brazilian families (total of 12). The results from such analysis do not suggest genetic heterogeneity for FSHD in our population. In 11 out of the 12 families studied with p13E-11, a shorter specific EcoRI band was found to segregate in all affected patients from each genealogy. In one family, the normal individuals had a smaller EcoRI fragment than the affected ones. The size of the EcoRI fragments detected with p13E-11 varied from 13.5 to 29 kb but was constant within each genealogy. Our results suggest that the use of the marker p13E-11 for preclinical and prenatal diagnosis should be done only in families in which it is possible to identify the fragments segregating among the affected individuals.