Service interruption on Monday 11 July from 12:30 to 13:00: all the sites of the CCSD (HAL, Epiciences, SciencesConf, AureHAL) will be inaccessible (network hardware connection).
Skip to Main content Skip to Navigation
Journal articles

Dysregulation of 4q35- and muscle-specific genes in fetuses with a short D4Z4 array linked to facio-scapulo-humeral dystrophy

Abstract : Facio-scapulo-humeral dystrophy (FSHD) results from deletions in the subtelomeric macrosatellite D4Z4 array on the 4q35 region. Upregulation of the DUX4 retrogene from the last D4Z4 repeated unit is thought to underlie FSHD pathophysiology. However, no one knows what triggers muscle defect and when alteration arises. To gain further insights into the molecular mechanisms of the disease, we evaluated at the molecular level, the perturbation linked to the FSHD genotype with no a priori on disease onset, severity or penetrance and prior to any infiltration by fibrotic or adipose tissue in biopsies from fetuses carrying a short pathogenic D4Z4 array (n 5 6) compared with fetuses with a non-pathogenic D4Z4 array (n 5 21). By measuring expression of several muscle-specific markers and 4q35 genes including the DUX4 retrogene by an RT-PCR and western blotting, we observed a global dysregulation of genes involved in myogenesis including MYOD1 in samples with <11 D4Z4. The DUX4-fl pathogenic transcript was detected in FSHD biopsies but also in controls. Importantly, in FSHD fetuses, we mainly detected the non-spliced DUX4-fl isoform. In addition, several other genes clustered at the 4q35 locus are upregulated in FSHD fetuses. Our study is the first to examine fetuses carrying an FSHD-linked genotype and reveals an extensive dysregulation of several muscle-specific and 4q35 genes at early development stage at a distance from any muscle defect. Overall, our work suggests that even if FSHD is an adult-onset muscular dystrophy, the disease might also involve early molecular defects arising during myogenesis or early differentiation.
Complete list of metadata

Cited literature [44 references]  Display  Hide  Download
Contributor : Stephane Roche Connect in order to contact the contributor
Submitted on : Tuesday, January 2, 2018 - 12:41:29 PM
Last modification on : Saturday, June 25, 2022 - 11:28:43 PM
Long-term archiving on: : Tuesday, April 3, 2018 - 12:15:57 PM


Files produced by the author(s)



Natacha Broucqsault, Julia Morere, Marie-Cécile Gaillard, Julie Dumonceaux, Julia Torrents, et al.. Dysregulation of 4q35- and muscle-specific genes in fetuses with a short D4Z4 array linked to facio-scapulo-humeral dystrophy. Human Molecular Genetics, Oxford University Press (OUP), 2013, 22 (20), pp.4206 - 4214. ⟨10.1093/hmg/ddt272⟩. ⟨hal-01662672⟩



Record views


Files downloads