Genetic modifiers of upper limb function in Duchenne muscular dystrophy
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 05, 2022
- Source ID
- 10.1007/s00415-022-11133-8
Entities
People
- Adele D’amico
- Angela Berardinelli
- Antonella Pini
- Aurora Fusto
- Chiara Panicucci
- Claudio Bruno
- Craig M. McDonald
- Daniele Sabbatini
- Elena Pegoraro
- Eleonora Diella
- Enrico Bertini
- Eric Hoffman
- Eugenio Mercuri
- Francesca Magri
- Giacomo P Comi
- Gianluca Vita
- Giovanni Baranello
- Grazia D’angelo
- Guja Astrea
- Heather Gordish-Dressman
- Joanna Janik
- Lauren Morgenroth
- Luca Bello
- Luisa Politano
- Marika Pane
- Matteo Villa
- Riccardo Masson
- Roberta Battini
- Sara Vianello
- Sonia Messina
- Stefano C. Previtali
- Tina Duong
- Tiziana Mongini
Organizations
- Fondazione Cariparo
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute on Disability, Independent Living, and Rehabilitation Research
- Parent Project Muscular Dystrophy
- Telethon Foundation
- United States Department of Defense