Mathula Thangarajh1, Luca Bello2, Heather Gordish-Dressman3. 1. Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA. 2. Department of Neurosciences DNS, University of Padova, Padova, Italy. 3. Center for Genetic Medicine, Children's Research Institute, Children's National Health System, Washington, District of Columbia, USA.
Abstract
INTRODUCTION/AIMS: There is considerable heterogenicity in clinical outcomes in Duchenne muscular dystrophy (DMD). The aim of this study was to assess whether dystrophin gene (DMD) pathogenic variant location influences upper or lower extremity motor function outcomes in a large prospective cohort. METHODS: We used longitudinal timed and quantitative motor function measurements obtained from 154 boys with DMD over a 10-y period by the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS) to understand how the trajectories of motor function differ based on proximal versus distal DMD pathogenic variants. Proximal variants were defined as located proximal to 5' DMD intron 44, and distal variants as those including nucleotides 3' DMD including intron 44. Distal DMD variants are predicted to alter the expression of short dystrophin isoforms (Dp140, Dp116, and Dp71). We compared various upper extremity and lower extremity motor function measures in these two groups, after adjusting for total lifetime corticosteroid use. RESULTS: The time to loss-of-ambulation and timed motor function measurements of both upper and lower limbs over a 10-y period were comparable between boys with proximal (n = 53) and distal (n = 101) DMD pathogenic variants. Age had a significant effect on several motor function outcomes. Boys younger than 7 y of age (n = 49) showed gain in function whereas boys 7 y and older (n = 71) declined, regardless of dystrophin pathogenic variant location. DISCUSSION: The longitudinal decline in upper and lower motor function is independent of proximal versus distal location of DMD pathogenic variants.
INTRODUCTION/AIMS: There is considerable heterogenicity in clinical outcomes in Duchenne muscular dystrophy (DMD). The aim of this study was to assess whether dystrophin gene (DMD) pathogenic variant location influences upper or lower extremity motor function outcomes in a large prospective cohort. METHODS: We used longitudinal timed and quantitative motor function measurements obtained from 154 boys with DMD over a 10-y period by the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS) to understand how the trajectories of motor function differ based on proximal versus distal DMD pathogenic variants. Proximal variants were defined as located proximal to 5' DMD intron 44, and distal variants as those including nucleotides 3' DMD including intron 44. Distal DMD variants are predicted to alter the expression of short dystrophin isoforms (Dp140, Dp116, and Dp71). We compared various upper extremity and lower extremity motor function measures in these two groups, after adjusting for total lifetime corticosteroid use. RESULTS: The time to loss-of-ambulation and timed motor function measurements of both upper and lower limbs over a 10-y period were comparable between boys with proximal (n = 53) and distal (n = 101) DMD pathogenic variants. Age had a significant effect on several motor function outcomes. Boys younger than 7 y of age (n = 49) showed gain in function whereas boys 7 y and older (n = 71) declined, regardless of dystrophin pathogenic variant location. DISCUSSION: The longitudinal decline in upper and lower motor function is independent of proximal versus distal location of DMD pathogenic variants.
Authors: Craig M McDonald; Erik K Henricson; Richard T Abresch; Tina Duong; Nanette C Joyce; Fengming Hu; Paula R Clemens; Eric P Hoffman; Avital Cnaan; Heather Gordish-Dressman Journal: Lancet Date: 2017-11-22 Impact factor: 79.321
Authors: Nathalie Doorenweerd; Chiara S Straathof; Eve M Dumas; Pietro Spitali; Ieke B Ginjaar; Beatrijs H Wokke; Debby G Schrans; Janneke C van den Bergen; Erik W van Zwet; Andrew Webb; Mark A van Buchem; Jan J Verschuuren; Jos G Hendriksen; Erik H Niks; Hermien E Kan Journal: Ann Neurol Date: 2014-07-24 Impact factor: 10.422
Authors: Mathula Thangarajh; Jos Hendriksen; Michael P McDermott; William Martens; Kimberly A Hart; Robert C Griggs Journal: Neurology Date: 2019-10-08 Impact factor: 9.910
Authors: Mathula Thangarajh; Christopher F Spurney; Heather Gordish-Dressman; Paula R Clemens; Eric P Hoffman; Craig M McDonald; Erik K Henricson Journal: PLoS Curr Date: 2018-10-17
Authors: Pietro Spitali; Irina Zaharieva; Francesco Muntoni; Annemieke Aartsma-Rus; Stefan Bohringer; Monika Hiller; Amina Chaouch; Andreas Roos; Chiara Scotton; Mireille Claustres; Luca Bello; Craig M McDonald; Eric P Hoffman; Zaida Koeks; H Eka Suchiman; Sebahattin Cirak; Mariacristina Scoto; Mojgan Reza; Peter A C 't Hoen; Erik H Niks; Sylvie Tuffery-Giraud; Hanns Lochmüller; Alessandra Ferlini Journal: Eur J Hum Genet Date: 2020-01-02 Impact factor: 4.246