2.Diagnostic Significance of Immunohistochemical Staining in Muscular Dystrophy.
Journal of the Korean Neurological Association 2006;24(1):1-13
Muscular dystrophy (MD) is a heterogeneous group of inherited muscle disorders caused by the mutations of different genes encoding muscle proteins, and it is now classified according to the results of the linkage analysis and the genes or proteins affected. Except for some subtypes of MD presenting with characteristic manifestations, differential diagnosis is always a challenging task to clinicians because of the similarities in clinical features and muscle pathology findings between subtypes. The immunohistochemical stain (IHC) using a biopsied skeletal muscle is an effective and simplest way to identify defective proteins in MD, so that we can classify MD into its subtypes and target the affected gene. The frozen muscle sections are used for the IHC, and specialized procedures of fixation, blocking, antibody reaction, and detection are serially performed. By using sets of commercially available antibodies, we can identify many different subtypes of MD, which include dystrophinopathies, several forms of limb-girdle muscular dystrophies, and subgroups of congenital muscular dystrophies. Although each disease shows its own characteristic patterns on IHC, there are some exceptional cases including normal expression of the mutated protein and secondary loss of the unaffected protein. Since the quality of the IHC results largely depends on technique and experience, the choice of antibody panel for IHC should be individualized in each laboratory considering the number of muscle biopsy requests, available technicians, and expenses for the study.
Antibodies
;
Biopsy
;
Diagnosis, Differential
;
Immunohistochemistry
;
Muscle Proteins
;
Muscle, Skeletal
;
Muscular Diseases
;
Muscular Dystrophies*
;
Muscular Dystrophies, Limb-Girdle
;
Pathology
3.Magnetic resonance imaging for the diagnosis of muscular dystrophy.
Jing TANG ; Jia-Peng ZHANG ; Xue-Jun YANG ; Jing-Zi ZHONG ; Yan-Shu XIE ; Qi MENG ; Dan LAN
Chinese Journal of Contemporary Pediatrics 2022;24(11):1231-1237
OBJECTIVES:
To summarize the skeletal muscle magnetic resonance imaging (MRI) features of the lower limbs in common subtypes of muscular dystrophy (MD) and the experience in the application of MRI in the diagnosis of MD.
METHODS:
A total of 48 children with MD who were diagnosed by genetic testing were enrolled as subjects. The muscle MRI features of the lower limbs were analyzed. Cumulative fatty infiltration score was calculated for each subtype, and the correlation of cumulative fatty infiltration score with clinical indices was analyzed for Duchenne muscular dystrophy (DMD).
RESULTS:
DMD was characterized by the involvement of the gluteus maximus and the adductor magnus. Becker muscular dystrophy was characterized by the involvement of the vastus lateralis muscle. Limb-girdle muscular dystrophy was characterized by the involvement of the adductor magnus, the vastus intermedius, the vastus medialis, and the vastus lateralis muscle. For DMD, the cumulative fatty infiltration score of the lower limb muscles was significantly correlated with age, course of the disease, muscle strength, and motor function (P<0.05), while it was not significantly correlated with the serum creatine kinase level (P>0.05).
CONCLUSIONS
Different subtypes of MD have different MRI manifestations, and MRI may help with the diagnosis and assessment of MD.
Child
;
Humans
;
Muscular Dystrophy, Duchenne/diagnostic imaging*
;
Muscular Dystrophies, Limb-Girdle/pathology*
;
Muscle, Skeletal/diagnostic imaging*
;
Magnetic Resonance Imaging/methods*
;
Thigh/pathology*
4.Progression of GNE Myopathy Based on the Patient-Reported Outcome
Young Eun PARK ; Dae Seong KIM ; Young Chul CHOI ; Jin Hong SHIN
Journal of Clinical Neurology 2019;15(3):275-284
BACKGROUND AND PURPOSE: GNE myopathy is a rare progressive myopathy caused by biallelic mutations in the GNE gene, and frequently accompanied by rimmed vacuoles in muscle pathology. The initial symptom of foot drop or hip-girdle weakness eventually spreads to all limbs over a period of decades. Recent advances in pathophysiologic research have facilitated therapeutic trials aimed at resolving the core biochemical defect. However, there remains unsettled heterogeneity in its natural course, which confounds the analysis of therapeutic outcomes. We performed the first large-scale study of Korean patients with GNE myopathy. METHODS: We gathered the genetic and clinical profiles of 44 Korean patients with genetically confirmed GNE myopathy. The clinical progression was estimated retrospectively based on a patient-reported questionnaire on the status of the functional joint sets and daily activities. RESULTS: The wrist and neck were the last joints to lose antigravity functionality irrespective of whether the weakness started from the ankle or hip. Two-thirds of the patients could walk either independently or with an aid. The order of losing daily activities could be sorted from standing to eating. Patients with limb-girdle phenotype showed an earlier age at onset than those with foot-drop onset. Patients with biallelic kinase domain mutations tended to progress more rapidly than those with epimerase and kinase domain mutations. CONCLUSIONS: The reported data can guide the clinical management of GNE myopathy, as well as provide perspective to help the development of clinical trials.
Age of Onset
;
Ankle
;
Disease Progression
;
Eating
;
Extremities
;
Foot
;
Hip
;
Humans
;
Joints
;
Muscular Diseases
;
Muscular Dystrophies, Limb-Girdle
;
Neck
;
Pathology
;
Phenotype
;
Phosphotransferases
;
Population Characteristics
;
Retrospective Studies
;
Surveys and Questionnaires
;
Vacuoles
;
Wrist
6.Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations.
Hyung Jun PARK ; Hoon JANG ; Jung Hwan LEE ; Ha Young SHIN ; Sung Rae CHO ; Kee Duk PARK ; Duhee BANG ; Min Goo LEE ; Seung Min KIM ; Ji Hyun LEE ; Young Chul CHOI
Yonsei Medical Journal 2016;57(1):173-179
PURPOSE: This study was designed to investigate the characteristics of Korean patients with calpainopathy. MATERIALS AND METHODS: Thirteen patients from ten unrelated families were diagnosed with calpainopathy via direct or targeted sequencing of the CAPN3 gene. Clinical, mutational, and pathological spectra were then analyzed. RESULTS: Nine different mutations, including four novel mutations (NM_000070: c.1524+1G>T, c.1789_1790inA, c.2184+1G>T, and c.2384C>T) were identified. The median age at symptom onset was 22 (interquartile range: 15-28). Common clinical findings were joint contracture in nine patients, winged scapula in four, and lordosis in one. However, we also found highly variable clinical features including early onset joint contractures, asymptomatic hyperCKemia, and heterogeneous clinical severity in three members of the same family. Four of nine muscle specimens revealed lobulated fibers, but three showed normal skeletal muscle histology. CONCLUSION: We identified four novel CAPN3 mutations and demonstrated clinical and pathological heterogeneity in Korean patients with calpainopathy.
Adolescent
;
Adult
;
Amino Acid Sequence
;
Asian Continental Ancestry Group/*genetics
;
Calpain/*genetics
;
Female
;
Genetic Testing
;
Humans
;
Male
;
Molecular Sequence Data
;
Muscle Proteins/*genetics
;
Muscle, Skeletal/pathology
;
Muscular Dystrophies, Limb-Girdle/ethnology/*genetics/*pathology
;
*Mutation
;
Republic of Korea
7.Heterogeneous Characteristics of Korean Patients with Dysferlinopathy.
Hyung Jun PARK ; Ji Man HONG ; Gyoung Im SUH ; Ha Young SHIN ; Seung Min KIM ; Il Nam SUNWOO ; Bum Chun SUH ; Young Chul CHOI
Journal of Korean Medical Science 2012;27(4):423-429
Dysferlinopathy is caused by mutations in the DYSF gene. To characterize the clinical spectrum, we investigated the characteristics of 31 Korean dysferlinopathy patients confirmed by immunohistochemistry. The mean age of symptom onset was 22.23 +/- 7.34 yr. The serum creatine kinase (CK) was highly increased (4- to 101-fold above normal). The pathological findings of muscle specimens showed nonspecific dystrophic features and frequent inflammatory cell infiltration. Muscle imaging studies showed fatty atrophic changes dominantly in the posterolateral muscles of the lower limb. The patients with dysferlinopathy were classified by initial muscle weakness: fifteen patients with Miyoshi myopathy phenotype (MM), thirteen patients with limb girdle muscular dystrophy 2B phenotype (LGMD2B), two patients with proximodistal phenotype, and one asymptomatic patient. There were no differences between LGMD2B and MM groups in terms of onset age, serum CK levels and pathological findings. Dysferlinopathy patients usually have young adult onset and high serum CK levels. However, heterogeneity of clinical presentations and pathologic findings upon routine staining makes it difficult to diagnose dysferlinopathy. These limitations make immunohistochemistry currently the most important method for the diagnosis of dysferlinopathy.
Adolescent
;
Adult
;
Age of Onset
;
Creatine Kinase/blood
;
Distal Myopathies/pathology
;
Female
;
Humans
;
Immunohistochemistry
;
Male
;
Membrane Proteins/genetics
;
Middle Aged
;
Muscle Proteins/genetics
;
Muscular Atrophy/pathology
;
Muscular Dystrophies, Limb-Girdle/*diagnosis/genetics/pathology
;
Mutation
;
Phenotype
;
Republic of Korea
;
Tomography, X-Ray Computed
;
Young Adult
8.Differential Immunohistological Features of Inflammatory Myopathies and Dysferlinopathy.
Jae Hwan CHOI ; Yeong Eun PARK ; Sung Il KIM ; Jeong Il KIM ; Chang Hoon LEE ; Kyu Hyun PARK ; Dae Seong KIM
Journal of Korean Medical Science 2009;24(6):1015-1023
This study was performed in order to characterize the types of the infiltrating cells, and the expression profiles of major histocompatibility complex (MHC) class I and membrane attack complex (MAC) in patients with inflammatory myopathies and dysferlinopathy. Immunohistochemical stains were performed using monoclonal antibodies against several inflammatory cell types, MHC class I, and MAC in muscles from inflammatory myopathies and dysferlinopathy. There was significant difference in the types of infiltrating cells between polymyositis (PM), dermatomyositis (DM), and dysferlinopathy, including significantly high CD4+/CD8+ T cell ratio and B/T cell ratio in DM. In dysferlinopathy, CD4+ T cells were the most abundant and the proportions of infiltrating cell types were similar to those of DM. MHC class I was expressed in muscle fibers of PM and DM regardless of the presence of inflammatory infiltrates. MAC was expressed in necrotic fibers and vessels of PM and DM. One patient with early stage DM had a MAC deposits on endomysial capillaries. In dysferlinopathy, MAC deposit was also observed on the sarcolemma of nonnecrotic fibers. The analysis of inflammatory cells, MHC class I expressions and MAC deposits may help to differentiate dysferlinopathy from idiopathic inflammatory myopathy.
Adult
;
Aged
;
*Dermatomyositis/immunology/pathology
;
Female
;
Genes, MHC Class I
;
Humans
;
Male
;
*Membrane Proteins/genetics/immunology
;
Middle Aged
;
Muscle Fibers, Skeletal/cytology/immunology/pathology
;
*Muscle Proteins/genetics/immunology
;
*Muscular Dystrophies, Limb-Girdle/immunology/pathology
;
*Myositis/immunology/pathology
;
*Polymyositis/immunology/pathology
;
T-Lymphocytes/cytology/immunology/pathology
;
Young Adult