Physical mapping evidence for a duplicated region on chromosome 10qter showing high homology with the facioscapulohumeral muscular dystrophy locus on chromosome 4qter.

p13E-11, a probe (D4F104S1 locus) derived from chromosome 4q35, detects EcoRI-rearranged fragments less than 28 kb in both sporadic and familial cases of facioscapulohumeral muscular dystrophy (FSHD). These fragments are smaller than those observed in healthy individuals. The interpretation of Southern blots is complicated by the fact that p13E-11 reveals two pairs of polymorphic alleles, one 4q35-specific and the other unlinked to 4q35, that sometimes overlap each other. We cloned a non-4q35 13-kb fragment not related to the disease from a sporadic FSHD patient of Italian origin. Haplotype analysis and in situ hybridization experiments showed that this fragment was located on the 10qter region. Restriction mapping of the 10qter clone, when compared with the 4q35 fragment, indicates a similar arrangement of KpnI tandemly repeated units and flanking sequences. However 4q35 and 10q26 EcoRI clones can be distinguished by restriction analysis with SfiI and StyI. This observation could be exploited for future applications in the field of molecular diagnosis and genetic counseling. In addition the isolation of two 10q26 cosmid clones (D10S1484 and D10S1485) from a human genomic library and the construction of a detailed physical map, spanning about 40 kb, showed that the structural homology extended upstream of the EcoRI sites, suggesting that a duplicated FSHD locus resided in the subtelomeric region of the long arm of chromosome 10. We cannot exclude the involvement of the duplicated locus in the molecular mechanism of the disease and in the genetic heterogeneity of FSHD syndromes.