LONGITUDINAL STUDY OF THE RELATIONSHIP BETWEEN IMPAIRMENT, ACTIVITY LIMITATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will establish the largest comprehensive longitudinal assessment of individuals with Duchenne muscular dystrophy, and it will be the first that uses the World Health Organization''s new framework on the International Classification of Functioning, Health and Disability. It will also longitudinally assess the psychosocial impact of the disease as it progresses on the affected persons with DMD and their families. The study will longitudinally examine the relationship between impairment, secondary conditions, activity limitation, participation and quality of life. In addition the study will evaluate the psychosocial impact of DMD in a large cohort of subjects. Regression analyses will determine the modifying effects of impairment, activities, participation and demographic data on quality of life. Successful development of an extensive and broad database will allow the performance of longitudinal prospective rehabilitation research, and evaluation of broad interventions in relation to quality of life outcomes in neuromuscular disorders. Also, the study will investigate single nucleotide polymorphisms (SNPs) in DMD patients to see how genetic variability potentially influences the efficacy of corticosteroid treatment in DMD. In addition, this project will provide a model for future multicenter efforts focusing on rehabilitation research for other neuromuscular diseases. Outcomes of this work will reach males with DMD and their families and may impact future public health policies that will positively affect their quality of life. Long term assessment of patients with DMD will reveal new physical and psychosocial characteristics related to the progression of the disease that will aid in diagnosis and treatment and facilitate improvements in patient quality of life. Also, analysis of genetic variability among DMD patients will provide new information related to improving DMD therapy. Phenotyping Study Aims Aim 1: Longitudinally assess body function and body structure (impairment) through the measurement of anthropometrics, muscle strength and pulmonary function in subjects with DMD through the multicenter CINRG network. Aim 2: Longitudinally assess activity limitations in subjects with DMD through CINRG with timed motor performance, burden of care, and functional status. Aim 3: Longitudinally assess secondary conditions in subjects with DMD. Aim 4: Longitudinally assess participation, life satisfaction, service utilization and health-related quality of life in subjects with DMD. Aim 5: Determine appropriate outcome measurements for impairment, activities (activity limitations), participation and quality of life to determine the effect of prednisone and other therapeutic interventions on these factors. Aim 6: Using the most robust impairment, activity, participation and quality of life outcome measures, determine the sample size, power and statistical methods for the analysis of the effect size for future planned randomized-controlled rehabilitation interventions in DMD. SNP Genotyping Study Aims Our goal of this the proposed study is to define polygenic modifiers of disease progression, and also response to treatment with glucocorticoids (prednisone and deflazacort). The most common type of human genetic variation is the single-nucleotide polymorphism (SNP), a base position at which two alternative bases occur at an appreciable frequency (>1%) in the population. SNPs are 90% of variation in the human genome. SNPs occur on the average of 1 per 1000 to 2000 bp throughout the 3.2 billion bp of the human genome while coding region SNPs (cSNPs) occur on the average of 1 per 346 bp.