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Genetic modifiers of upper limb function in Duchenne muscular dystrophy

Sabbatini, Daniele; Fusto, Aurora; Vianello, Sara; Villa, Matteo; Janik, Joanna; D'Angelo, Grazia; Diella, Eleonora; ... Pegoraro, Elena; + view all (2022) Genetic modifiers of upper limb function in Duchenne muscular dystrophy. Journal of Neurology , 269 pp. 4884-4894. 10.1007/s00415-022-11133-8. Green open access

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Abstract

Genetic modifiers of Duchenne muscular dystrophy (DMD) are variants located in genes different from the disease-causing gene DMD, but associated with differences in disease onset, progression, or response to treatment. Modifiers described so far have been tested mainly for associations with ambulatory function, while their effect on upper limb function, which is especially relevant for quality of life and independence in non-ambulatory patients, is unknown. We tested genotypes at several known modifier loci (SPP1, LTBP4, CD40, ACTN3) for association with Performance Upper Limb version 1.2 score in an Italian multicenter cohort, and with Brooke scale score in the Cooperative International Neuromuscular Group Duchenne Natural History Study (CINRG-DNHS), using generalized estimating equation (GEE) models of longitudinally collected data, with age and glucocorticoid treatment as covariates. CD40 rs1883832, previously linked to earlier loss of ambulation, emerged as a modifier of upper limb function, negatively affecting shoulder and distal domains of PUL (p = 0.023 and 0.018, respectively) in the Italian cohort, as well as of Brooke score (p = 0.018) in the CINRG-DNHS. These findings will be useful for the design and interpretation of clinical trials in DMD, especially for non-ambulatory populations.

Type: Article
Title: Genetic modifiers of upper limb function in Duchenne muscular dystrophy
Location: Germany
Open access status: An open access version is available from UCL Discovery
DOI: 10.1007/s00415-022-11133-8
Publisher version: https://doi.org/10.1007/s00415-022-11133-8
Language: English
Additional information: © 2022 Springer Nature Switzerland AG. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).
Keywords: Duchenne muscular dystrophy, Genetic modifiers, Upper limb function, SPP1-osteopontin, CD40
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10149604
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