Summary Facioscapulohumeral muscular dystrophy (FSHD) can be subdivided into two types: FSHD1, caused by contraction of the D4Z4 repeat on chromosome 4q35, and FSHD2, caused by mild contraction of the D4Z4 repeat plus aberrant hypomethylation mediated by genetic variants in SMCHD1, DNMT3B , or LRIF1 . Genetic diagnosis of FSHD is challenging because of the complex procedures required. Here, we applied Nanopore CRISPR/Cas9-targeted resequencing for the diagnosis of FSHD by simultaneous detection of D4Z4 repeat length and methylation status at nucleotide level in genetically-confirmed and suspected patients. We found significant hypomethylation of contracted D4Z4 repeats in FSHD1 and strong correlation between methylation rate and patient phenotype. This finding can explain how repeat contraction contributes to disease pathogenesis by activating DUX4 expression.
We aimed to evaluate the diagnostic accuracy of enzyme-linked immunosorbent assay (ELISA) for anti-muscle specific tyrosine kinase (MuSK) antibody (Ab) in a large cohort of anti-acetylcholine receptor (AChR) Ab-negative generalized myasthenia gravis (MG), and also to investigate clinical contexts for the diagnosis of MuSK MG.A retrospective study of 160 patients with a clinical suspicion of AChR Ab-negative generalized MG was performed. The serum samples were tested for anti-clustered AChR Ab by cell-based assay (CBA), anti-MuSK Ab by ELISA, CBA and/or radioimmunoprecipitation assay (RIPA). Clinical data were compared between anti-MuSK Ab-positive MG and double seronegative (AChR and MuSK) MG groups.After excluding non-MG and clustered AChR Ab-positive patients, we identified 89 patients as a cohort of AChR Ab-negative generalized MG. Anti-MuSK Ab was positive by ELISA in 22 (24.7%) patients. While CBA identified five additional anti-MuSK Ab-positive patients, the results of ELISA were mostly consistent with CBA and RIPA with Cohen's kappa of 0.80 and 0.90, respectively (p < 0.001). The most frequent differential diagnosis was motor neuron disease particularly of bulbar onset which showed remarkably overlapping clinical and electrophysiological features with MuSK MG at presentation.While confirming the highest sensitivity of CBA for detecting anti-MuSK Ab, our results highlight the clinical pitfalls in making a diagnosis of MuSK MG and may support a diagnostic utility of MuSK-ELISA in clinical practice.
Abstract: Schisandrae fructus (SF) has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1–10 µg/mL) of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 µg/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged with sarcopenia and the patients with disuse atrophy. Keywords: Schisandrae fructus, mTOR signaling, human skeletal muscle cells, myotubes
Background: For the differential diagnosis between the various subtypes of muscular dystrophy, the analysis of the protein expression pattern from the biopsied skeletal muscle tissue is essential. Authors performed the immunohistochemical study (IHC) using sets of antibodies for the differentiation of subtypes of muscular dystrophy. Methods: Antibodies against dystrophin C-terminal, dystrophin rod domain, dystrophin N-terminal, -, -, -sarcoglycans, laminin 2 chain, dysferlin, and -dystroglycan were used for the IHC study in 43 patients with muscular dystrophy. The reactivity against the specific antibodies was graded and the clinical findings were assessed. Results: We found 15 cases of dystrophin deficiency and 7 cases of dysferlin deficiency. Those with dystrophin deficiency were clinically classified previously as follows, 11 cases with Duchenne's muscular dystrophy (DMD), two with congenital muscular dystrophy (CMD), one with Becker's muscular dystrophy (BMD), and a female patient with limb-girdle muscular dystrophy (LGMD). Those with dysferlin deficiency consisted of 4 cases with LGMD phenotype and 3 with distal myopathy. Conclusions: The results of our study confirm the dystrophin immunostain is essential for the identification of dystrophinopathies among the various subtypes of muscular dystrophy. Also, the identification of 7 cases with dysferlin deficiency suggests dysferlinopathy is the common cause of muscular dystrophy in Korea.
Collagen-VI-related myopathies are caused by mutations in the COL6A1, COL6A2, and COL6A3 and are known to have a wide phenotypic spectrum, including Bethlem myopathy, Ullrich congenital muscular dystrophy, intermediate phenotype, and limb-girdle muscular dystrophy. These patients present with joint hyperextensibility and/or contractures as well as skin changes and muscle weakness, and so clinicians need to notice those extramuscular symptoms in order to achieve a correct diagnosis. We describe the clinical, pathological, and radiological features in a family with Bethlem myopathy caused by a COL6A1 mutation. Key Words: Collagen VI, Bethlem myopathy, Phenotype
Ullrich congenital muscular dystrophy (UCMD) is caused by mutations in one of three genes encoding collagen VI. Although UCMD usually shows an early onset, progressive weakness, contractures and hyperlaxity of the joints, and respiratory failure, it is well known to exhibit a wide spectrum of clinical severities. The severities of the phenotypic subtypes are mainly divided according to the ambulation status. We report a patient with the early-severe phenotype of UCMD who was diagnosed by the detection of novel recessive mutations in COL6A1.
Several studies on clinical practice for Duchenne muscular dystrophy (DMD) have been conducted in Western countries. However, there have been only a few similar studies in Asia and Oceania. Here, we investigate the steroid therapy-related clinical practice for DMD among the local experts. In 2015, we conducted a DMD expert survey in Asia and Oceania to acquire information regarding patients with DMD and to assess current clinical practice with the cooperation of Asian and Oceanian Myology Centre, a neuromuscular disease research network.We obtained survey responses from 87 out of 148 clinicians (62%) from 13 countries and regions. In China, 1385 DMD patients were followed-up by 5 respondent neurologists, and 84% were between 0 and 9 years of age (15% were 10-19 years, 1% > 19 years). While in Japan, 1032 patients were followed-up by 20 clinicians, and the age distribution was similar between the 3 groups (27% were 0-9 years, 35% were 10-19 years, 38% were >19 years). Most respondent clinicians (91%) were aware of DMD standard of care recommendations. Daily prednisolone/prednisone administration was used most frequently at initiation (N = 45, 64%). Inconsistent opinion on steroid therapy after loss of ambulation and medication for bone protection was observed.Rare disease research infrastructures have been underdeveloped in many of Asian and Oceanian countries. In this situation, our results show the snapshots of current medical situation and clinical practice in DMD. For further epidemiological studies, expansion of DMD registries is necessary.
'%3e%3cg id='b'%3e%3cpath id='a' stroke='%23000' stroke-width='2' d='M-6-25H6m-12 3H6m-12 3H6'/%3e%3cuse xlink:href='%23a' y='44'/%3e%3c/g%3e%3cpath stroke='%23fff' d='M0 17v10'/%3e%3ccircle r='12' fill='%23cd2e3a'/%3e%3cpath fill='%230047a0' d='M0-12A6 6 0 0 0 0 0a6 6 0 0 1 0 12 12 12 0 0 1 0-24z'/%3e%3c/g%3e%3cg transform='rotate(-123.69)'%3e%3cuse xlink:href='%23b'/%3e%3cpath stroke='%23fff' d='M0-23.5v3M0 17v3.5m0 3v3'/%3e%3c/g%3e%3c/svg%3e)
