Article (Scientific journals)
Newborn screening of duchenne muscular dystrophy specifically targeting deletions amenable to exon‑skipping therapy
BECKERS, Pablo; CABERG, Jean-Hubert; DIDEBERG, Vinciane et al.
2021In Scientific Reports, 11, p. 3011
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Keywords :
Duchenne muscular dystrophy; Neuromuscular disorders; Newborn screening
Abstract :
[en] Duchenne Muscular Dystrophy (DMD) is a lethal progressive muscle-wasting disease. New treatment strategies relying on DMD gene exon-skipping therapy have recently been approved and about 30% of patients could be amenable to exon 51, 53 or 45 skipping. We evaluated the spectrum of deletions reported in DMD registries, and designed a method to screen newborns and identify DMD deletions amenable to exon 51, 53 and 45 skipping. We developed a multiplex qPCR assay identifying hemi(homo)-zygotic deletions of the flanking exons of these therapeutic targets in DMD exons (i.e. exons 44, 46, 50, 52 and 54). We conducted an evaluation of our new method in 51 male patients with a DMD phenotype, 50 female carriers of a DMD deletion and 19 controls. Studies were performed on dried blood spots with patient’s consent. We analyzed qPCR amplification curves of controls, carriers, and DMD patients to discern the presence or the absence of the target exons. Analysis of the exons flanking the exon-skipping targets permitted the identification of patients that could benefit from exon-skipping. All samples were correctly genotyped, with either presence or absence of amplification of the target exon. This proof-of-concept study demonstrates that this new assay is a highly sensitive method to identify DMD patients carrying deletions that are rescuable by exon-skipping treatment. The method is easily scalable to population-based screening. This targeted screening approach could address the new management paradigm in DMD, and could help to optimize the beneficial therapeutic effect of DMD therapies by permitting pre-symptomatic care.
Disciplines :
Laboratory medicine & medical technology
Author, co-author :
BECKERS, Pablo ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Pool assistant - biologie clinique
CABERG, Jean-Hubert ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Unité de laboratoire - neurogénétique
DIDEBERG, Vinciane ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Laboratoire génétique moléculaire
Dangouloff, Tamara  ;  Université de Liège - ULiège > Département des sciences cliniques > Neuropédiatrie
den Dunnen, Johan T.
BOURS, Vincent ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Service de génétique
Servais, Laurent ;  Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
BOEMER, François  ;  Centre Hospitalier Universitaire de Liège - CHU > Unilab > Laboratoire Biochimie Génétique
Language :
English
Title :
Newborn screening of duchenne muscular dystrophy specifically targeting deletions amenable to exon‑skipping therapy
Publication date :
04 February 2021
Journal title :
Scientific Reports
eISSN :
2045-2322
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
11
Pages :
3011
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 05 March 2021

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