Effects of genetic variants on lower leg muscle fat fraction evaluated with MRI in Beckers muscular dystrophy


Topic:

Translational Research

Poster Number: LB433

Author(s):

Pratiksha Pranil Awale, BPth, MS, PhD candidate, University of Florida, Alison M Barnard, PT, DPT, PhD, University of Florida, Kelly E Rock, University of Florida, Rebecca Willcocks, PhD, University of Florida, S H Subramony, MD, University of Florida, Donovan J Lott, PT, PhD, University of Florida, Bill Rooney, PhD, Oregon Health & Science University, Glenn A Walter, PhD, University of Florida, Krista H Elvire Vandenborne, PhD, University of Florida, Sean Charles Forbes, PhD, University of Florida

Introduction: Becker muscular dystrophy (BMD) is characterized by heterogenous disease involvement due, in part, to the genetic variant in the dystrophin gene. Understanding genotype-phenotype relationships are important for understanding disease progression and developing therapies. Objective: The purpose of this study was to examine lower leg muscle fat fraction (FF) in different genetic variants of BMD. Methods: We recruited ambulatory (n=24) and non-ambulatory (n=5) participants with BMD (n=29; age:19-65 years) between Dec 2021-January 2025 and evaluated them using 3-T MR systems. Three-point Dixon imaging was used to measure FF of lower leg muscles, focusing on the medial gastrocnemius (MG) and tibialis anterior (TA) muscles due to their faster and slower progression, respectively. We compared muscle FF between individuals with deletions versus duplications, as well as between individuals with different exonic deletions. Results: 83% of participants had single or multiple exon deletions with the most common genotype being a deletion of exons 45-47 (n=7). No differences were observed in TA and MG muscle FF between individuals with duplications vs deletions. When comparing different deletions, six out of seven participants with exon 45-47 deletions and one out of four with exon 45-48 had higher MG FFs(FF>0.6), while the three other individuals with exon 45-48, two individuals with 48-51 and 49-51 all had lower MG FFs (FF<0.5). Similarly, four out of seven with 45-47 deletion had TA FF ≥0.2, while all the remaining individuals with exon 45-47, 45-48,48-51, and 49-51 had FF <0.2. Conclusions: Our findings are consistent with exon deletions 45-47 being a more severe phenotype compared to exon 45-48 and exon X-51 deletions, in agreement with functional data in recent papers. These findings support that MRI FF is a valuable tool for non-invasively evaluating genetic variants in BMD, and they provide insight into exon skipping therapeutic approaches in Duchenne muscular dystrophy.