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

The gene responsible for facioscapulohuineral muscular dystrophy(FSHD), an autosomal dominant neuromuscular condition, has beenmapped to chromosome 4. Until recently, the two closest availablemarkers were D4S139 and D4S163 but a new marker (p13E-11) whichrecognizes de novo rearrangements in isolated cases of FSHDcharacterized by shorter EcoRI fragments has been now identified.Linkage analysis In FSHD families with pl3E4l shows that usuallya smaller fragment segregates with the disease gene among theaffected individuals from each genealogy. In the present paper,we report the results from linkage analysis with the markerloci D4S163 and D4S139 in 6 FSHID families and with pl3E-11in these and In 6 other additional Brazilian families (totalof 12). The results from such analysis do not suggest geneticheterogeneity for FSHD in our population. In 11 out of the 12families studied with pl3E-11, a shorter specific EcoRI bandwas found to segregate In all affected patients from each genealogy.In one family, the normal Individuals had a smaller EcoRI fragmentthan the affected ones. The size of the EcoRI fragments detectedwith pl3E-11 varied from 13.5 to 29 kb but was constant withineach genealogy. Our results suggest that the use of the markerpl3E-11 for predlinical and prenatal diagnosis should be doneonly in families in which it is possible to identify the fragmentssegregating among the affected individuals.