BACKGROUND: Dysferlin is a 230 kDa protein of the sarcolemma. This encoding gene is mutated in patients with dysferlinopathy (limb-girdle muscular dystrophy 2B and Miyoshi myopathy), which is characterized byan active muscle degeneration and regeneration process. Dysferlin is known to play an essential role in muscle signaling and muscle fiber repair. We studied the gene to define its functional role in muscle repair and differentiation in human skeletal muscle of the patients with myopathies and cultured human myoblast. METHODS: An immunohistochemical analysis of dysferlin and N-CAM in biopsied muscle tissue obtained from eleven patients with myopathies [six patients with Duchenne muscular dystrophy (DMD), two patients with dermatomyositis (DM), two patients with polymyositis (PM), and one patient with dysferlinopathy (MM)] and eight normal controls. Cultured human myoblast obtained from normal muscle tissue was also analyzed by the expression of dysferlin through immunocytochemical staining and western blot. RESULTS: The immunoreactivity of dysferlin was strongly expressed in regenerative muscle fibers of myopathies except dysferlinpathy, which was co-localization with N-CAM by double immunohistochemistry. By western blot analysis, the expression level of dysferlin was variable in myopathies compared to normal controls, but no expression in dyferlinopathy. The expression of dysferlin in myotubes was significantly increased compared to that in myoblast by immunostaining and western blot analysis. CONCLUSIONS: These results indicated that the expression of dysferlin increased in regenerative and degenerative muscle fibers and also increased in myoblast differentiation. Our study supports that dysferlin not only has a role in skeletal muscle development but also in regeneration/repair process.
Blotting, Western ; Dermatomyositis ; Humans ; Humans* ; Immunohistochemistry ; Muscle Fibers, Skeletal ; Muscle, Skeletal* ; Muscular Diseases* ; Muscular Dystrophies ; Muscular Dystrophy, Duchenne ; Myoblasts ; Polymyositis ; Regeneration ; Sarcolemma

The real-time ultrasonography is a simple, noninvasive procedure that is most suitable for application in pediatric practice. The ultrasonographic appearance of various disorders in children such as progressive muscular dystrophies, infantile spinal muscular atrophy, congenital myopathies, and motor neuropathies has been found to be strikingly abnormal. We have done a pilot study using real-time ultrasonography in children with Duchenne muscular dystrophy in an attempt to correlate their clinicopathologic profiles with scan findings. Echogenicity and delineation of fascia at midthigh and midcalf muscle were measured using a real-time linear array ultrasound scanner in 12 Duchenne mucular dystrophy patients attending our Muscle Clinic, as a double-blind pilot study matched against 10 controls. The ultrasonic scan findings in normal children revealed no echogenicity of muscle, distinct echogenicity of bone and delineation of fascia. But all Duchenne muscular dystrophy patients had increased echogenicity of muscle and decreased echogenicity of bone, and some patients had interruption of delineation of fascia. Duchenne muscular dystrophy patients who were unable to raise from standard height chair showed higher grade of echogenicity at midthigh level than the patients who were able to raise from standard height chair. But this result was not applicable at midcalf level. We concluded that the real-time ultrasonography was useful diagnosis method in Duchenne muscular dystrophy. In addition, when the real-time B ultrasonography was applied to midthigh level, the ultrasonic scan findings could reflect indirectly the functional ability of Duchenne muscular dystrophy patients.
Child ; Diagnosis ; Fascia ; Humans ; Muscular Diseases ; Muscular Dystrophies ; Muscular Dystrophy, Duchenne* ; Pilot Projects ; Spinal Muscular Atrophies of Childhood ; Ultrasonics ; Ultrasonography*

OBJECTIVE: To evaluate pulmonary functions of patients with amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), and myotonic muscular dystrophy (MMD) at the onset of ventilatory insufficiency. METHODS: This retrospective study included ALS, DMD, and MMD patients with regular outpatient clinic follow-up in the Department of Rehabilitation Medicine at Gangnam Severance Hospital before the application of non-invasive positive pressure ventilation (NIPPV). The patients were enrolled from August 2001 to March 2014. If patients experienced ventilatory insufficiency, they were treated with NIPPV, and their pulmonary functions were subsequently measured. RESULTS: Ninety-four DMD patients, 41 ALS patients, and 21 MMD patients were included in the study. The mean SpO2 was lower in the MMD group than in the other two groups. The mean forced vital capacity (FVC) in the supine position was approximately low to mid 20% on average in DMD and ALS patients, whereas it was 10% higher in MMD patients. ALS patients showed a significantly lower FVC in the supine position than in the sitting position. Maximal insufflation capacity, unassisted peak cough flow, maximum inspiratory pressure (MIP), and maximum expiratory pressure (MEP) were significantly higher in MMD group than in the other groups. MEP was significantly the lowest in DMD patients, followed by in ALS, and MMD patients, in order. CONCLUSION: Disease-specific values of pulmonary function, including FVC, MEP, and MIP, can be accurately used to assess the onset of ventilatory insufficiency in patients with ALS, DMD, and MMD.
Ambulatory Care Facilities ; Amyotrophic Lateral Sclerosis* ; Cough ; Follow-Up Studies ; Humans ; Insufflation ; Muscular Dystrophies* ; Muscular Dystrophy, Duchenne* ; Myotonic Dystrophy ; Neuromuscular Diseases ; Positive-Pressure Respiration ; Rehabilitation ; Respiratory Insufficiency ; Retrospective Studies ; Supine Position ; Vital Capacity

Progressive muscular dystrophy (PMD) is an X-linked recessive primary muscular disease characterized by progressive muscular weakness. It causes gait disturbance and complications such as pneumonia, heart failure, and aspiration, so lead to death. Becker muscular dystrophy (BMD) is a milder type of PMD, of which incidence is 5 cases per 100,000 populations. It begins later and evolves more slowly than Duchenne muscular dystrophy (DMD). In PMD patients without heart failure symptom, there may be ECG abnormality or ventricular dilatation, impaired ventricular function which is consistent with dilated cardiomyopathy, especially in DMD. In BMD, heart failure is rare but ECG or echocardiographic abnormality is often found. With the advance of molecular genetics, mutations of the dystrophin gene is proved to be related to the pathogenesis of PMD and dilated cardiomyopathy. We confirmed the deletion of exon 43-51 in the dystrophin gene a case of BMD with asymptomatic dilated cardiomyopathy, diagnosed by echocardiography.
Cardiomyopathy, Dilated ; Dilatation ; Dystrophin* ; Echocardiography ; Electrocardiography ; Exons* ; Gait ; Heart Failure ; Humans ; Incidence ; Molecular Biology ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophies ; Muscular Dystrophy, Duchenne* ; Pneumonia ; Ventricular Function

Progressive muscular dystrophy (PMD) is an X-linked recessive primary muscular disease characterized by progressive muscular weakness. It causes gait disturbance and complications such as pneumonia, heart failure, and aspiration, so lead to death. Becker muscular dystrophy (BMD) is a milder type of PMD, of which incidence is 5 cases per 100,000 populations. It begins later and evolves more slowly than Duchenne muscular dystrophy (DMD). In PMD patients without heart failure symptom, there may be ECG abnormality or ventricular dilatation, impaired ventricular function which is consistent with dilated cardiomyopathy, especially in DMD. In BMD, heart failure is rare but ECG or echocardiographic abnormality is often found. With the advance of molecular genetics, mutations of the dystrophin gene is proved to be related to the pathogenesis of PMD and dilated cardiomyopathy. We confirmed the deletion of exon 43-51 in the dystrophin gene a case of BMD with asymptomatic dilated cardiomyopathy, diagnosed by echocardiography.
Cardiomyopathy, Dilated ; Dilatation ; Dystrophin* ; Echocardiography ; Electrocardiography ; Exons* ; Gait ; Heart Failure ; Humans ; Incidence ; Molecular Biology ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophies ; Muscular Dystrophy, Duchenne* ; Pneumonia ; Ventricular Function

PURPOSE: To perform and compare differential diagnosis of patients with thyroid-associated myopathy, idiopathic orbital myositis and normal controls based on orbital computed tomography. Orbital fat and extraocular muscle densities were quantified using Hounsfield Unit (HU) and their characteristics were compared and analyzed. METHODS: From February 2005 to January 2013, orbital computed tomography was performed on 90 eyes of 47 thyroid-associated myopathy patients, 18 eyes of 14 idiopathic orbital myositis patients and 280 eyes of 140 normal subjects. The average values of orbital fat and extraocular muscle densities were measured and compared using HU. The density differences between the patients with thyroid-associated myopathy and the normal group were analyzed by age, clinical activity score, ocular protrusion and disease duration. RESULTS: In the thyroid-associated myopathy group, orbital fat and extraocular muscle densities were -87.8 +/- 12.5 HU and 48.7 +/- 7.1 HU, respectively. In the idiopathic orbital myositis group, the orbital fat and extraocular muscle densities were 79.9 +/- 9.9 HU and 49.2 +/- 9.1 HU, respectively. There was a statistically significant lower result of orbital fat in the thyroid-associated myopathy group (p = 0.002), however, the extraocular muscle density did not show a statistically significant difference (p = 0.775). The orbital fat and extraocular muscle densities of the normal group were -79.0 +/- 11.2 HU and 54.3 +/- 6.3 HU, respectively. There were significantly lower results in both orbital fat and extraocular muscle densities in the thyroid-associated myopathy group than normal group (p = 0.000). In active cases and those accompanied by ocular protrusion, there was no significant difference in orbital fat density (p = 0.345 and p = 0.952, respectively), while extraocular muscle density significantly decreased (p = 0.007 and p = 0.003, respectively). CONCLUSIONS: A difference between the orbital fat and extraocular muscle densities in thyroid-associated myopathy and idiopathic orbital myositis could be quantitatively found using HU and orbital computed tomography.
Diagnosis, Differential ; Humans ; Muscles* ; Muscular Diseases* ; Orbit* ; Orbital Myositis*

PURPOSE: The authors have experienced thirty three children of progressive muscular dystrophy. 10 children of these(30.3%) were considered as chronic hepatitis because of persistent, unexplained elevated serum aminotransferase values. We performed this study in order to evaluate the characteristics of age distribution, clinical and histologic features in children considered as chronic hepatitis. METHODS: This study was performed on thirty three children of progressive muscular dystrophy from Febrary, 1983 to June, 1992. 10 children of these(30.3%) were considered as chronic hepatitis because of persistent, unexplained elevated serum aminotransferase values. These 10 children were referred to our pediatric gastroenterologic department for studies of liver diseases. Hepatitis viral marker studies were negative in all of them. We performed serum CK concentration, the most useful marker of progressive muscular dystrophy, then confirmation of diagnosis was made by EMG and muscle biopsy in most of them. RESULTS: 1) 10 children (30.3%) were considered as chronic hepatitis. 2) 6 cases of 7 (85.7%) before 3 years of age were considered as chronic hepatitis 3) All of them were absence of clinical symptom and sign on admission but later recognized Gowers?sign and muscle weakness in 2 cases over 10 years of age after detailed physical examination. 4) We performed muscle biopsy in 6 cases of 10 children considered as chronic hepatitis. 5 cases were Duchenne muscular dystrophy and 1 cases was Becker muscular dystrophy. CONCLUSIONS: We concluded that pediatrician need to consider progressive muscular dystrophy when faced with persistent, unexplained serum aminotransferase elevation. In this situations, measurement of serum CK concentration and careful physical examination are the most important and useful means of correctly identifying progressive muscular dystrophy.
Age Distribution ; Biomarkers ; Biopsy ; Child ; Diagnosis ; Hepatitis ; Hepatitis, Chronic* ; Humans ; Liver Diseases ; Muscle Weakness ; Muscular Dystrophies* ; Muscular Dystrophy, Duchenne ; Physical Examination

OBJECTIVETo establish a specific technique for diagnosing and classifying Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), facioscapulohumeral muscular dystrophy (FSHD) and neurologic dystrophy.

METHODSForty-seven cases were detected by immunofluorescence technique for analyzing dystrophin located in skeletal muscle cell membrane with the use of mouse monoclonal antibodies, goat and rabbit polyclonal antibodies.

RESULTSThe normal individuals showed ringed positive staining stripe around muscle fibers. Negative result of staining was seen in 16 DMD patients. Eleven BMD patients had discontinuous or a patchy positive staining pattern, and all of 10 FSHD and 10 neurological amyotrophic patients showed positive dystrophin staining.

CONCLUSIONDetecting dystrophin in the skeletal muscle cell membrane of muscular patients is an efficient technique for diagnosing and classifying various types of muscular dystrophy.

Adolescent ; Adult ; Child ; Child, Preschool ; Diagnosis, Differential ; Dystrophin ; analysis ; Female ; Fluorescent Antibody Technique ; methods ; Humans ; Male ; Muscle, Skeletal ; chemistry ; pathology ; Muscular Dystrophies ; diagnosis ; metabolism ; Muscular Dystrophy, Duchenne ; diagnosis ; metabolism ; Muscular Dystrophy, Facioscapulohumeral ; diagnosis ; metabolism ; Neuromuscular Diseases ; diagnosis ; metabolism

OBJECTIVETo elucidate the usefulness of next generation sequencing for diagnosis of inherited myopathy, and to analyze the relevance between clinical phenotype and genotype in inherited myopathy.

METHODRelated genes were selected for SureSelect target enrichment system kit (Panel Version 1 and Panel Version 2). A total of 134 patients who were diagnosed as inherited myopathy clinically underwent next generation sequencing in Department of Pediatrics, Peking University First Hospital from January 2013 to June 2014. Clinical information and gene detection result of the patients were collected and analyzed.

RESULTSeventy-seven of 134 patients (89 males and 45 females, visiting ages from 6-month-old to 26-year-old, average visiting age was 6 years and 1 month) underwent next generation sequencing by Panel Version 1 in 2013, and 57 patients underwent next generation sequencing by Panel Version 2 in 2014. The gene detection revealed that 74 patients had pathogenic gene mutations, and the positive rate of genetic diagnosis was 55.22%. One patient was diagnosed as metabolic myopathy. Five patients were diagnosed as congenital myopathy; 68 were diagnosed as muscular dystrophy, including 22 with congenital muscular dystrophy 1A (MDC1A), 11 with Ullrich congenital muscular dystrophy (UCMD), 6 with Bethlem myopathy (BM), 12 with Duchenne muscular dystrophy (DMD) caused by point mutations in DMD gene, 5 with LMNA-related congenital muscular dystrophy (L-CMD), 1 with Emery-Dreifuss muscular dystrophy (EDMD), 7 with alpha-dystroglycanopathy (α-DG) patients, and 4 with limb-girdle muscular dystrophy (LGMD) patients.

CONCLUSIONNext generation sequencing plays an important role in diagnosis of inherited myopathy. Clinical and biological information analysis was essential for screening pathogenic gene of inherited myopathy.

Adolescent ; Child ; Child, Preschool ; Contracture ; DNA Mutational Analysis ; Female ; Genetic Diseases, Inborn ; diagnosis ; genetics ; Genetic Testing ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Male ; Molecular Diagnostic Techniques ; Muscular Diseases ; diagnosis ; genetics ; Muscular Dystrophies ; congenital ; Muscular Dystrophies, Limb-Girdle ; Muscular Dystrophy, Duchenne ; Muscular Dystrophy, Emery-Dreifuss ; Mutation ; Phenotype ; Sclerosis ; Walker-Warburg Syndrome ; Young Adult

Becker muscular dystrophy is a X-linked recessive disease with the affected gene at locus Xp21, characterized by progressive muscular weakness. Without the definite family history, it has been known that the diagnosis of this disease is almost impossible on clinical grounds alone. We reviewed the muscle pathology of two casses of genetically confirmed Becker muscular dystrophy to know the diagnositc significances of this study. The first case, a 20 year old man, is the classical one with definite family history of X-linked recessive heredity. The muscle pathology of the biceps showed dystrophic muscular changes, including increased internal nuclei, marked variation of fiber sizes and mild endomysial fibrosis. The dystrophin stain of the muscle was also confirmative for the diagnosis. The second case was a 32 year old man who has been biopsied his left vastus lateralis 5 years before this genetic diagnosis. This case is a sporadic one without the family history. The diagnosis at the time of muscle biopsy was limb-girdle muscular dystorphy or inclusion body myositis because of the typical rimmed vacuoles and marked variation of fiber sizes. The dystophin stain was not available at that time. Our conclusion is that the molecular genetic study and/or dystrophin protein test of muscle biopsy should be done in every clinically suspected patient, including limb-girdle muscular dystorphy, inclusion body myositis or rimmed vacuolar myopathies.
Adult ; Biopsy ; Diagnosis ; Dystrophin ; Fibrosis ; Heredity ; Humans ; Incontinentia Pigmenti* ; Molecular Biology ; Muscle Weakness ; Muscular Diseases ; Muscular Dystrophy, Duchenne ; Myositis, Inclusion Body ; Pathology ; Quadriceps Muscle ; Vacuoles ; Young Adult