Key result
A de novo D4Z4 repeat exchange between chromosomes 4 and 10 caused FSHD in two families via DUX4 expression from chromosome 10, confirming DUX4 derepression as the principal disease pathway.
Why the study?
Due to the position of the D4Z4 repeat near the telomere and the complex aetiology of FSHD, there is ongoing debate regarding whether transcriptional deregulation of closely linked genes is involved in FSHD pathogenesis.
Case-Control
Demonstrates that FSHD can occur on chromosome 10 due to interchromosomal rearrangement, providing evidence that DUX4 derepression is the dominant disease pathway.
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Broadens FSHD genetic mechanisms to chromosome 10; confirms DUX4 derepression as dominant pathway but leaves diagnostic implications open.
Lemmers et al. (2021) conducted a case-control in Facioscapulohumeral dystrophy (FSHD). D4Z4 repeat exchange between chromosomes 4 and 10 vs. Control individuals was evaluated on DUX4 and DUX4 target gene expression. A de novo D4Z4 repeat exchange between chromosomes 4 and 10 caused FSHD in two families via DUX4 expression from chromosome 10, confirming DUX4 derepression as the principal disease pathway.
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