The FSHD-linked locus D4F104S1 (p13E-11) on 4q35 has a homologue on 10qter

Facioscapulohumeral muscular dystrophy (FSHD) has recently been shown to be associated with deletions that are detectable using probe p13E-11 (D4F104S1). Although these deletions reside within large, highly polymorphic restriction fragments (20-300 kb), the "mutant" fragment is usually shorter than 28 kb and can routinely be detected using conventional agarose gel electrophoresis. Yet, the complete visualization of the alleles requires pulsed-field gel electrophoresis (PFGE). Family studies showed that p13E-11 detects two nonallelic loci in this size range, only one of which originates from chromosome 4q35. We have assigned the other p13E-11 locus to chromosome 10qter by linkage analysis in CEPH pedigrees. Knowing the location of both loci improves the diagnostic reliability, as the exact origin of "small" EcoRI fragments can be determined by haplotyping. Since FSHD shows genetic heterogeneity, this 10qter locus became an interesting candidate to be the second FSHD locus. However, analysis of a large chromosome 4-unlinked FSHD family did not provide evidence for linkage on chromosome 10qter.