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

Abstract

Please be advised that this information was generated on 2018-05-08 and may be subject to change.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 vi sualization 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 lOqter 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 ge netic 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 chro mosome 10qter>

Facioscapulohumeral Muscular Dystrophy: From Clinical Data to Molecular Genetics and Return

“…The repeat element at 10q is 98% identical to D4Z4 at 4q, and the size of 10q EcoRI alleles varies between 11 and 300 kb (1-100 D4Z4 units). Moreover, 10% of these alleles are shorter than 35 kb (8 D4Z4 units) (Bakker et al, 1996;Bakker et al, 1995), overlapping the 4q alleles. Clearly these overlapping features can interfere with the molecular diagnosis of FSHD.…”

Facioscapulohumeral Muscular Dystrophy As a Model for Epigenetic Regulation and Disease

“…Not surprisingly, these large deletions of subtelomeric macrosatellite DNA in FSHD1 correlate with epigenetic changes at 4q35, discussed next, which appear to be essential for developing disease (40,160). It is interesting to note that chromosome 10q26 contains a subtelomeric D4Z4 macrosatellite that is highly homologous to the array at 4q35 (5,41); however, FSHD1 is linked only to contractions on chromosome 4 and D4Z4 contractions at 10q26 are non-pathogenic (99,100,130,181). Thus, in combination with the clinical diagnosis, the genetic diagnosis for FSHD1 is a contraction at 4q35 to 1-11 D4Z4 repeats, in cis with a permissive 4qA subtelomere.…”

Diagnostic approach for FSHD revisited: SMCHD1 mutations cause FSHD2 and act as modifiers of disease severity in FSHD1

“…10,11 Contractions on 10q are not associated with the disease. 11,12 In about 5% of patients fulfilling the clinical criteria of FSHD, no contraction of the D4Z4 repeat array can be found. No clinical signs have been identified yet to distinguish these patients from FSHD1.…”