TY - JOUR
T1 - Duchenne Muscular Dystrophy from Brain to Muscle
T2 - The Role of Brain Dystrophin Isoforms in Motor Functions
AU - Wijekoon, Nalaka
AU - Gonawala, Lakmal
AU - Ratnayake, Pyara
AU - Amaratunga, Dhammika
AU - Hathout, Yetrib
AU - Mohan, Chandra
AU - Steinbusch, Harry W.M.
AU - Dalal, Ashwin
AU - Hoffman, Eric P.
AU - de Silva, K. Ranil D.
N1 - Funding Information:
The corresponding author in Sri Lanka received funding from the Muscular Dystrophy Association, Washington DC, USA (grant number FMS/7090/2010), the World Health Organization (WHO) (grant number 2010/81594-0), the World Class University Grant Project (University of Sri Jayewardenepura, Sri Lanka, grant numbers WCUP/Ph.D./19/2013 and WCUP/Ph.D./19B 2013), the Ministry of Primary Industries, Sri Lanka (grant number SP/CIN/2016/02), the University of Sri Jayewardenepura (grant numbers ASP/06/RE/2010/07, ASP/06/RE/2012/18, ASP/06/RE/2013/28), General Sir John Kotelawala Defence University, Sri Lanka (grant numbers KDU/RG/2021/CARE/005 and KDU/RG/2021/CARE/006), and the Interdisciplinary Center for Innovation in Biotechnology and Neuroscience, University of Sri Jayewardenepura (ICIBN/USJ). The equipment was donated by the National Institutes of Health (Bethesda, MD, USA) through IBRO-APRC and by the Chinese Neuroscience Society. Moreover, the corresponding author has received funding from IBRO-APRC and the International Society for Neurochemistry (ISN) for international training scholarships for postgraduates and to conduct neuroscience workshops in Sri Lanka.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/9/1
Y1 - 2023/9/1
N2 - Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, “standing on one leg R”, “standing on one leg L”, and “walk”, declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial.
AB - Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, “standing on one leg R”, “standing on one leg L”, and “walk”, declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial.
KW - DMD
KW - genotype–phenotype
KW - muscular dystrophy
KW - natural history
KW - South Asia
U2 - 10.3390/jcm12175637
DO - 10.3390/jcm12175637
M3 - Article
SN - 2077-0383
VL - 12
JO - Journal of Clinical Medicine
JF - Journal of Clinical Medicine
IS - 17
M1 - 5637
ER -