scholarly journals N-CAM expression: The study of muscle disease in a tertiary center of Thailand

2020 ◽  
Author(s):  
Kanyarat Laoyoung ◽  
Phu Waisayarat ◽  
Charungthai Dejthevaporn ◽  
Chaiyos Khongkhatithum ◽  
Jariya Waisayarat
Keyword(s):  
Muscular Dystrophy ◽  
Mitochondrial Myopathy ◽  
Inflammatory Myopathy ◽  
Muscle Disease ◽  
P Value ◽  
Thai Population ◽  
Muscle Diseases ◽  
Tertiary Center ◽  
Chi Squared ◽  
The Mean

Abstract Objectives To evaluate the correlation between N-CAM expression and diagnosis of common muscle diseases in the Thai population.Methods The expression of N-CAM was interpreted in 75 muscle biopsy specimens diagnosed with myopathies in a 3-year retrospective study. We used anti-CD56 (MRQ-42) rabbit monoclonal primary antibody (1:200, Cell Marque, MilliporeSigma, Rocklin, CA, USA) in our immunohistochemical study.Results Of our 75 patients, 41 cases were female and 34 were male. The mean age of the patients was 35-year-old, with the range from 3 months to 83 years. 35 (46.67%) of the specimens were N-CAM-positive, and 40 (53.33%) were N-CAM-negative. There were 35 (46.67%) cases diagnosed with nonspecific myopathy, 17 (22.67%) with inflammatory myopathy, 9 (12.00%) with neurogenic dystrophy, 7 (9.33%) with muscular dystrophy, 5 (6.67%) with non-diagnostic myopathy, and 2 (2.67%) with mitochondrial myopathy. Chi-squared testing was used to analyze the N-CAM expression data and the diagnosis. There is a statistically significant correlation between inflammatory myopathy and N-CAM positivity (p-value <0.001, OR 14.250, 95% CI 2.960-68.606), with 15 out of 17 cases being N-CAM-positive. N-CAM was also positive in muscular dystrophy, neurogenic myopathy, and nonspecific myopathy but they were not statistically significant. We did not find N-CAM expression in our 2 mitochondrial myopathy cases, nor in the 5 non-diagnostic myopathy cases.Conclusion N-CAM expression can be a complementary tool for diagnostic evaluation in muscle diseases with regeneration or denervation of muscle fibers. We recommend further study in a larger group.

scholarly journals N-CAM expression: The study of muscle disease in a tertiary center of Thailand

2020 ◽  
Author(s):  
Kanyarat Laoyoung ◽  
Jariya Waisayarat
Keyword(s):  
Muscular Dystrophy ◽  
Mitochondrial Myopathy ◽  
Inflammatory Myopathy ◽  
Clinical Information ◽  
Muscle Disease ◽  
P Value ◽  
Muscle Fibres ◽  
Pathological Findings ◽  
Cell Surface Glycoprotein ◽  
Tertiary Center

Abstract Background The neural cell adhesion molecule (N-CAM), also called CD56, is a cell-surface glycoprotein that mediates intercellular adhesive interactions in the nervous system. N-CAM is expressed in neuromuscular endplates, nerves, satellite cells, and embryonic muscle, but it is lost as development proceeds and is nearly absent from adult muscle. N-CAM re-expression was detected in a denervated, regenerating and degenerated muscle fibres. Muscle disease or myopathy is diagnosed based on the presence of denervated, regenerating and degenerated fibres on muscle biopsy combined with clinical information. Some regenerating fibres looked like normal fibre and were challenging to identify but showed positive N-CAM staining. Objectives To explore the expression of N-CAM in muscle disease. Methods N-CAM expression and interpretation were performed in a 3-year retrospective study of 75 muscle biopsies diagnosed with myopathies. The pathological findings and clinical information were also thoroughly reviewed. Results Of 75 myopathy patients, 41 (55%) cases were female, and 34 (45%) cases were male. The mean age was 35 years. The range of age was 3 months to 83 years. The expression of N-CAM and clinical information, including pathological findings, were analyzed using Fisher’s exact versus chi-square tests. N-CAM expression data was performed in 75 samples, 35 (46.67%) were positive for N-CAM, and 40 (53.33%) were negative for N-CAM. The diagnosis of the muscle disease was nonspecific myopathy with 35 (46%) cases, inflammatory myopathy with 17 (23%) cases, neurogenic myopathy with 9 (12%) cases, muscular dystrophy with 7 (9%) cases, non-diagnostic myopathy with 5 (7%) cases, and mitochondrial myopathy with 2 (3%) cases. The inflammatory myopathy showed positive N-CAM in 15 out of 17 cases with statistical significance (p-value < 0.001, ORs (95% CI) 14.250 (2.960-68.606)). N-CAM was also positive in muscular dystrophy, neurogenic myopathy, and nonspecific myopathy but was not statistically significant in p-value. No positive N-CAM was found in mitochondrial myopathy and non-diagnostic myopathy. Conclusion N-CAM expression accompanied by the pattern of staining could be considered to help narrow down the differential diagnosis of myopathies. We recommend further study in a larger group.

scholarly journals Enzyme Histochemical Assessment of Mitochondrial Functions in Patients with Myopathic form of Limb-Girdle Syndrome

2011 ◽  
Vol 2011 ◽  
pp. 1-8
Author(s):  
Ritu Verma ◽  
Lily Pal ◽  
Rakesh Pandey ◽  
Vimal Kumar Paliwal
Keyword(s):  
Muscular Dystrophy ◽  
Mitochondrial Myopathy ◽  
Enzyme Histochemistry ◽  
Inflammatory Myopathy ◽  
Muscle Disease ◽  
Characteristic Appearance ◽  
Mitochondrial Functions ◽  
Hematoxylin And Eosin ◽  
Hematoxylin And Eosin Staining ◽  
Girdle Muscle

Isolated mitochondrial myopathy is characterized by slowly progressive limb-girdle muscle weakness and resembles other muscle disorders like muscular dystrophy or inflammatory myopathy on clinical grounds. Identification of abnormal mitochondria in the muscle tissue is required for the diagnosis of isolated mitochondrial myopathy. Therefore, this study was done with aim to identify patients with isolated mitochondrial myopathy among those with limb-girdle muscle syndromes of undefined cause. Forty-eight consecutive patients with limb-girdle muscle disease from 2008 to 2010 were screened for Duchenne/Becker muscular dystrophy gene deletion, metabolic myopathy, and drug-induced and endocrine causes. Twenty patients without an identifiable cause were subjected to muscle biopsy for hematoxylin and eosin staining and enzyme histochemistry. Clinical, biochemical, and electrophysiological features in all these patients with limb-girdle muscle disease were nonspecific, and no conclusion regarding the underlying cause could be drawn from these investigations. On hematoxylin and eosin staining, 12 patients were diagnosed as muscular dystrophy, inflammatory myopathy with characteristic appearance of polymyositis was diagnosed in 4 patients, and 3 patients had normal muscle histology. After enzyme histochemistry, one patient was identified having mitochondrial myopathy. A brief case summary of the only patient diagnosed as isolated mitochondrial myopathy in our study is presented.

Z-line degradation and phagocytosis of sarcomeric fragments in myonecrosis

1983 ◽  
Vol 41 ◽  
pp. 790-791
Author(s):  
Melinda L. Estes ◽  
Samuel M. Chou
Keyword(s):  
Vastus Lateralis ◽  
Inflammatory Myopathy ◽  
Muscle Disease ◽  
White Female ◽  
Inflammatory Cell Infiltrate ◽  
Limb Weakness ◽  
Muscle Diseases ◽  
History Of ◽  
The Right ◽  
Mononuclear Inflammatory Cell

Many muscle diseases show common pathological features although their etiology is different. In primary muscle diseases a characteristic finding is myofiber necrosis. The mechanism of myonecrosis is unknown. Polymyositis is a primary muscle disease characterized by acute and subacute degeneration as well as regeneration of muscle fibers coupled with an inflammatory infiltrate. We present a case of polymyositis with unusual ultrastructural features indicative of the basic pathogenetic process involved in myonecrosis.The patient is a 63-year-old white female with a one history of proximal limb weakness, weight loss and fatigue. Examination revealed mild proximal weakness and diminished deep tendon reflexes. Her creatine kinase was 1800 mU/ml (normal < 140 mU/ml) and electromyography was consistent with an inflammatory myopathy which was verified by light microscopy on biopsy muscle. Ultrastructural study of necrotizing myofiber, from the right vastus lateralis, showed: (1) degradation of the Z-lines with preservation of the adjacent Abands including M-lines and H-bands, (Fig. 1), (2) fracture of the sarcomeres at the I-bands with disappearance of the Z-lines, (Fig. 2), (3) fragmented sarcomeres without I-bands, engulfed by invading phagocytes, (Fig. 3, a & b ), and (4) mononuclear inflammatory cell infiltrate in the endomysium.

scholarly journals Genotype characterization and delayed loss of ambulation by glucocorticoids in a large cohort of patients with Duchenne muscular dystrophy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Shu Zhang ◽  
◽  
Dongdong Qin ◽  
Liwen Wu ◽  
Man Li ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Hazard Ratio ◽  
Large Cohort ◽  
Muscle Disease ◽  
Clinical Progression ◽  
Large Deletions ◽  
The Mean ◽  
Lower Hazard

Abstract Background Duchenne muscular dystrophy (DMD) is the most common genetic muscle disease in human. We aimed to describe the genotype distribution in a large cohort of Chinese DMD patients and their delayed loss of ambulation by glucocorticoid (GC) treatments. This is to facilitate protocol designs and outcome measures for the emerging DMD clinical trials. Results A total of 1163 patients with DMD were recruited and genotyped. Genotype variations were categorized as large deletions, large duplications, and small mutations. Large deletions were further analyzed for those amenable to exon-skipping therapies. Participants aged 5 years or older were grouped into GC-treated and GC-naïve groups. Clinical progression among different genotypes and their responses to GC treatments were measured by age at loss of ambulation (LOA). Among the mutation genotypes, large deletions, large duplications, and small mutations accounted for 68.79%, 7.14%, and 24.07%, respectively. The mean age at diagnosis was 4.59 years; the median ages at LOA for the GC-naïve, prednisone/prednisolone-treated, and deflazacort-treated groups were 10.23, 12.02, and 13.95 years, respectively. The “deletion amenable to skipping exon 44” subgroup and the nonsense-mutation subgroup had older ages at LOA than the “other deletions” subgroup. Subgroups were further analyzed by both genotypes and GC status. All genotypes showed significant beneficial responses to GC treatment. Deletions amenable to skipping exon 44 showed a lower hazard ratio (0.155). The mean age at death was 18.57 years in this DMD group. Conclusion Genotype variation influences clinical progression in certain DMD groups. Beneficial responses to GC treatment were observed among all DMD genotypes. Compared with other genotypes, deletions amenable to skipping exon 44 had a lower hazard ratio, which may indicate a stronger protective effect of GC treatments on this subgroup. These data are valuable for designing future clinical trials, as clinical outcomes may be influenced by the genotypes.

scholarly journals Duchenne Muscular Dystrophy - Family in a Crisis

1970 ◽  
pp. 36-39
Author(s):  
M Robed Amin ◽  
Chowdhury Chironjib Borua ◽  
Kaji Shafiqul Alam ◽  
Fazle Rabbi Chowdhury ◽  
Rabiul Jahan Sarkar ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Case Series ◽  
Dystrophin Gene ◽  
Muscle Disease ◽  
Motor Neuron Diseases ◽  
Muscle Diseases ◽  
Progressive Muscle Weakness ◽  
Recessive Disorders ◽  
Dystrophin Protein

Progressive muscular weakness with deformity leading to crippled states develop due to musculoskeletal and neurological disorders. Sometimes it is difficult to differentiate between primary muscle disease and neurological disease. But there is some classical presentation of muscle diseases which have its own entity and thus can be clinically differentiated from neurological disorder especially spinal cord and motor neuron diseases. Muscular dystrophy is one of those disorder with distinct clinical features. Muscular dystrophy refers to a group of genetic, hereditary muscle diseases that cause progressive muscle weakness. Most types of MD are multi-system disorders with manifestations in body systems including skeletal system, the heart, gastrointestinal and nervous systems, endocrine glands, skin, eyes and other organs. Duchenne muscular dystrophy (DMD), is inherited in an X-linked recessive pattern, meaning that the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes, and is thus considered sex-linked. Males are therefore affected by X-linked recessive disorders much more often than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Duchenne muscular dystrophy and Backers muscular dystrophy are caused by mutations of the gene for the dystrophin protein and lead to an overabundance of the enzyme creatine kinase. The dystrophin gene is the largest gene in humans. In this case series a family with three brothers suffering from Duchenne muscular dystrophy is described and review with literature was done.   doi:10.3329/jom.v10i3.2015 J Medicine 2009; 10 (Supplement 1): 36-39

scholarly journals Validation of Chemokine Biomarkers in Duchenne Muscular Dystrophy

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 827
Author(s):  
Michael Ogundele ◽  
Jesslyn S. Zhang ◽  
Mansi V. Goswami ◽  
Marissa L. Barbieri ◽  
Utkarsh J. Dang ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Early Stage ◽  
Wild Type Mouse ◽  
Muscle Disease ◽  
Mdx Mouse ◽  
Control Group ◽  
P Value ◽  
Glucocorticoid Treatment

Duchenne muscular dystrophy (DMD) is a progressive muscle disease involving complex skeletal muscle pathogenesis. The pathogenesis is triggered by sarcolemma instability due to the lack of dystrophin protein expression, leading to Ca2+ influx, muscle fiber apoptosis, inflammation, muscle necrosis, and fibrosis. Our lab recently used two high-throughput multiplexing techniques (e.g., SomaScan® aptamer assay and tandem mass tag-(TMT) approach) and identified a series of serum protein biomarkers tied to different pathobiochemical pathways. In this study, we focused on validating the circulating levels of three proinflammatory chemokines (CCL2, CXCL10, and CCL18) that are believed to be involved in an early stage of muscle pathogenesis. We used highly specific and reproducible MSD ELISA assays and examined the association of these chemokines with DMD pathogenesis, age, disease severity, and response to glucocorticoid treatment. As expected, we confirmed that these three chemokines were significantly elevated in serum and muscle samples of DMD patients relative to age-matched healthy controls (p-value < 0.05, CCL18 was not significantly altered in muscle samples). These three chemokines were not significantly elevated in Becker muscular dystrophy (BMD) patients, a milder form of dystrophinopathy, when compared in a one-way ANOVA to a control group but remained significantly elevated in the age-matched DMD group (p < 0.05). CCL2 and CCL18 but not CXCL10 declined with age in DMD patients, whereas all three chemokines remained unchanged with age in BMD and controls. Only CCL2 showed significant association with time to climb four steps in the DMD group (r = 0.48, p = 0.038) and neared significant association with patients’ reported outcome in the BMD group (r = 0.39, p = 0.058). Furthermore, CCL2 was found to be elevated in a serum of the mdx mouse model of DMD, relative to wild-type mouse model. This study suggests that CCL2 might be a suitable candidate biomarker for follow-up studies to demonstrate its physiological significance and clinical utility in DMD.

The Direct Interconversion of Glucose and Fructose in Human Skeletal Muscle with Special Reference to Childhood Muscular Dystrophy

1973 ◽  
Vol 44 (4) ◽  
pp. 321-334 ◽  
Author(s):  
D. A. Ellis ◽  
Jennifer M. Strickland ◽  
J. F. Eccleston
Keyword(s):  
Muscular Dystrophy ◽  
Muscle Fibre ◽  
Muscle Disease ◽  
Control Groups ◽  
Dystrophic Muscle ◽  
Metabolic Products ◽  
Nad Oxidoreductase ◽  
Major Route ◽  
The Mean ◽  
Female Carriers

1. Acid extracts of muscle-fibre preparations from human biopsies incubated with [U-14C]glucose were chromatographically analysed. 2. Radioactivity of fructose was significantly greater in muscle from childhood dystrophy patients and also in female carriers of the disease compared with normal, foetal, neurogenic muscle disease and polymyositis control groups. 3. Measurements of the activity of polyol-NADP oxidoreductase (EC 1.1.1.21) and L-iditol-NAD oxidoreductase (EC 1.1.1.14) in muscle extracts compared with the ability of extracts to dephosphorylate fructose 6-phosphate, indicated that the probable route of fructose formation from glucose is via glucitol. The mean activities of the two specified enzymes in dystrophic muscle showed 13- and 3–5-fold increases respectively compared with normal muscle, and smaller increases compared with other controls. 4. Direct comparison of labelling patterns following incubation of muscle-fibre preparations with d-[U-14C]glucose, d-[U-14C]fructose and d-[U-14C]glucitol showed that these three substances are rapidly interconvertible mutual major metabolic products, confirming the glucitol pathway as a major route of fructose formation. 5. [U-14C]fructose is readily metabolized by dystrophic muscle, excluding the possibility of its accumulation being the result of poor utilization. 6. Inhibition of polyol oxidoreductase in dystrophic muscle preparations by 3,3′-tetramethyleneglutarate drastically reduces the ability of the fibres to utilize [U-14C]-glucose, and prevents the formation of [14C]fructose. 7. Some implications of these results are discussed in relation to the pathogenesis of childhood muscular dystrophy.

Disease activity and damage in hospitalized lupus patients: a Sabah perspective

Lupus ◽  
2020 ◽  
Vol 29 (3) ◽  
pp. 344-350
Author(s):  
S Selvananda ◽  
Y Y Chong ◽  
R J Thundyil
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Damage Index ◽  
Asia Pacific ◽  
Systemic Autoimmune Disease ◽  
P Value ◽  
Systemic Lupus ◽  
Sledai Score ◽  
Tertiary Center ◽  
The Mean

Objective Systemic lupus erythematosus (SLE) is a complex multi-systemic autoimmune disease with variable levels of activity that may wax and wane within the same patient over the years. In view of the scarcity of data about lupus in the East Malaysian population, we aimed to study the disease activity and damage index in patients with SLE hospitalized in a tertiary center in Sabah, East Malaysia. Methods We retrospectively studied all patients with SLE admitted from 1 January 2013 to 31 December 2015. Demographic data, clinical features, treatment received, SLEDAI and SLICC/ACR (Systemic Lupus International Collaborating Clinics/American College of Rheumatology) criteria and outcomes were collected. Results There were 108 patients studied whereby 88.9% were females. They had a mean age of 31.4 ± 11.02 years at admission and were multiethnic in origin. The mean number of ACR criteria for SLE was 5.03 ± 1.5 at the time of diagnosis. There were 158 hospitalizations during the 3 years. The main causes of hospitalization were flare of SLE (66.5%), infection (57.6%), renal biopsy (15.5%) and others (11.4%). Active nephritis (65%), cutaneous (44.4%) and hematological involvement (40.2%) were the three commonest manifestations. There was concurrent flare of SLE and infection in 41.1% of the admissions. The mean SLEDAI score at admission was 10.8 ± 7.20, with a mean SLEDAI of 9.3 ± 6.9 in those without damage and 11.9 ± 7.21 in those with damage ( p-value = 0.026). The median SLICC score was 1 with a mean of 0.93 ± 1.07. There were nine deaths (5.6%) during the study period and all patients were females. Compared with those who survived, they had a significantly higher SLEDAI score of 15.80 ± 8.2 ( p-value = 0.0207) and a SLICC score of 2.70 ± 1.6 ( p-value <0.001). Conclusion SLE is more common among the indigenous population of Sabah, the Kadazan-Dusun, which has not been shown before this study. Disease characteristics were, however, similar to reports from the Asia-Pacific region. Acute flare of SLE and infection remained the main causes of admission and readmissions and was present in 44.4% of the mortalities in our cohort.

scholarly journals Consequences of COVID-19 Lockdown on Children and Their Pets: Dangerous Increase of Dog Bites among the Paediatric Population

Children ◽  
2021 ◽  
Vol 8 (8) ◽  
pp. 620
Author(s):  
Giovanni Parente ◽  
Tommaso Gargano ◽  
Marco Di Mitri ◽  
Sara Cravano ◽  
Eduje Thomas ◽  
...  
Keyword(s):  
Paediatric Population ◽  
Lower Limbs ◽  
P Value ◽  
Upper Limbs ◽  
Female Ratio ◽  
Dog Bites ◽  
Chi Squared ◽  
The Mean ◽  
Related Stress ◽  
Male To Female

Background: The SARS-CoV-2 pandemic has not only put our national health systems to the test, but it also notably hit the economy, the society and the psychology of the people. Our pets have been subjected to the pandemic related stress too. The aim of the study was to evaluate whether the stress induced on domestic dogs resulted in an increase of dog bites in the paediatric population. Methods: A retrospective study was conducted on all patients admitted to our paediatric emergency department for dog bite from January 2014 and December 2020. We compared the total mean dog bites of the years 2014–2019 and the mean number per single month with the respective 2020 data. The bites were divided between bites from family dogs and bites from stranger dogs. Continuous data were analysed using single sample t test while categorical values with chi-squared test, considering statistically significant a p value < 0.05. Results: From January 2014 to December 2019, we recorded a mean of 41 ± 5.9 dog bites (range: 30–46) of which a mean 13 ± 2.6 (range: 10–17) were due to family dogs (32%) and a mean of 28 ± 2.4 (range: 25–31) were due to stranger dogs (68%); the male-to-female ratio was 3:2 and 43% of the injuries concerned the head and face, 26% the lower limbs, 25% the upper limbs, 3% the genitalia and 3% the torso. From January 2020 to December 2020, 30 children were admitted for dog bites: 22 were from family dogs (73%) and 8 from stranger dogs (27%); the male-to-female ratio was 14:11 and 72% of the injuries concerned the head and face, 16% the upper limbs, 8% the lower limbs and 4% the torso. The 2020 data’s higher number of family dog bites compared with the mean of those in the 2014–2019 period was statistically significant (p < 0.01) such as the 2020 data’s lower number of stranger dog bites when compared with the mean number of stranger dog bites in the 2014–2019 period (p < 0.01). Between 2014 and 2019, a mean of 9 ± 2 (range: 6–12) of the wounds needed to be sutured (22%), while 32 ± 3 (range: 28–35) wounds were discharged after application of Steri Strips (78%). On the other hand, in 2020, 21 wounds needed to be sutured (70%), and 9 received just Steri Strips application (41%). The frequency distribution of the treatments required (stitches vs. Steri Strips) between the 2014 to 2019 period and the 2020 period was statistically significant (p < 0.0001). Conclusions: The number of family dog bites in children increased in 2020, especially during the lockdown period. Paediatricians should pay a lot of attention now more than ever to educate parents on the importance of always supervising children who are playing with dogs.

scholarly journals Comprehensive Multi-cohort Transcriptional Meta-analysis of Muscle Diseases Identifies a Signature of Disease Severity

2022 ◽  
Author(s):  
Christopher James Walsh ◽  
Jane Batt ◽  
Margaret Herridge ◽  
Sunita Mathur ◽  
Gary D Bader ◽  
...  
Keyword(s):  
Disease Severity ◽  
Meta Analysis ◽  
Disease Patient ◽  
Gene Signature ◽  
Muscle Disease ◽  
Additional Patient ◽  
Shoulder Abduction ◽  
P Value ◽  
Muscle Diseases ◽  
Muscle Biopsies

Abstract Muscle diseases share common pathological features suggesting common underlying mechanisms. We hypothesized there is a common set of genes dysregulated across muscle diseases compared to healthy muscle and that these genes correlate with severity of muscle disease. We performed meta-analysis of transcriptional profiles of muscle biopsies from human muscle diseases and healthy controls. Studies obtained from public microarray repositories fulfilling quality criteria were divided into six categories: i) Immobility, ii) inflammatory myopathies, iii) ICU acquired weakness (ICUAW), iv) congenital muscle diseases, v) chronic systemic diseases, vi) motor neuron disease. Patient cohorts were separated in discovery and validation cohorts retaining roughly equal proportions of samples for the disease categories. To remove bias towards a specific muscle disease category we repeated the meta-analysis five times by removing data sets corresponding to one muscle disease class at a time in a “leave-one-disease-out” analysis. We used 636 muscle tissue samples from 30 independent cohorts to identify a 52 gene signature (36 up-regulated and 16 down-regulated genes). We validated the discriminatory power of this signature in 657 muscle biopsies from 12 additional patient cohorts encompassing five categories of muscle diseases with an area under the receiver operating characteristic curve of 0.91, 83% sensitivity, and 85.3% specificity. The expression score of the gene signature inversely correlated with quadriceps muscle mass (r =-0.50, p-value = 0.011) in ICUAW and shoulder abduction strength (r=-0.77, p-value = 0.014) in amyotrophic lateral sclerosis (ALS). The signature also positively correlated with histologic assessment of muscle atrophy in ALS (r=0.88, p-value=1.62x10−3) and fibrosis in muscular dystrophy (Jonckheere trend test p-value = 4.45 x 10−9). Our results identify a conserved transcriptional signature associated with clinical and histologic muscle disease severity. Several genes in this conserved signature have not been previously associated with muscle disease severity.

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