Fig. 2

Schematic representation of the D4Z4 region in atypical FSHD and non-FSHD cases. In the duplication type, although one D4Z4 repeat array is contracted, traditional Southern blotting may misinterpret the duplicated units as a single long repeat array, masking the contraction. While D4Z4 repeats exist throughout the genome, a similar repeat array occurs on chromosome 10q. Contractions in 10qD4Z4 alone do not cause FSHD; however, translocation of a permissive 4qA allele to the 10q locus can result in 10q-linked FSHD. In the D4Z4 proximally extended deletion (DPED) cases, a large proximal deletion removes the Southern blot probe region, making detection of the pathogenic allele difficult. In mosaicism, only a fraction of somatic cells harbour D4Z4-contracted alleles, leading to DUX4 expression and FSHD symptoms that are typically milder than in contraction-matched cases without mosaicism