Blog Archives
Angiotensin II receptor blocker losartan exacerbates muscle damage and exhibits weak blood pressure-lowering activity in a dysferlin-null model of LGMD 2B
There is no cure or beneficial management option for Limb-Girdle muscular dystrophy (MD) type 2B (LGMD2B). Losartan, a blood pressure (BP) lowering angiotensin II (AngII) receptor type 1 (ATR1) blocker (ARB) with unique anti-transforming growth factor-β (TGF-β) properties, can protect muscles in various types of MD such as Duchenne MD, suggesting a potential benefit for … [Read more]
Dilated cardiomyopathy and limb-girdle muscular dystrophy-dystroglycanopathy due to novel pathogenic variants in the DPM3 gene
Deficiency of Dolichol-P-mannose synthase subunit 3 (DPM3) affects the N-glycosylation and O-mannosylation pathways that are respectively involved in congenital disorders of glycosylation (CDG) and alpha-dystroglycanopathies. Herein, the researchers, including researchers from the Institute of Myology, describe novel pathogenic variants in the DPM3 gene in two unrelated male patients. They developed dilated cardiomyopathy in their late … [Read more]
Assessing the barriers to cardiac care in carriers of DMD and BMD
Duchenne and Becker muscular dystrophy (DBMD) are X-linked conditions causing progressive muscle weakness, muscle wasting, and cardiomyopathy in affected males. Two-thirds of cases of DBMD are inherited from a carrier female while one-third of cases occur sporadically. Women who are DBMD carriers typically do not manifest noticeable muscular symptoms. However, about 10% may develop cardiomyopathy … [Read more]
DMPK gene DNA methylation levels are associated with muscular and respiratory profiles in DM1
The objective of this study was to assess the effects of dystrophia myotonica protein kinase (DMPK) DNA methylation (DNAme) epivariation on muscular and respiratory profiles in patients with myotonic dystrophy type 1 (DM1). Phenotypes were assessed with standardized measures. Pyrosequencing of bisulfite-treated DNA was used to quantify DNAme levels in blood from 90 patients with … [Read more]
Late-onset thymidine kinase 2 deficiency: a review of 18 cases
TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the ‘myopathic form’ of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity. The authors describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with … [Read more]
Idiopathic inflammatory myopathy: Interrater variability in muscle biopsy reading
The objective of this study was to determine interrater variability in diagnosing individual muscle biopsy abnormalities and diagnosis. The authors developed a scoring tool to analyze consensus in muscle biopsy reading of an ad hoc workgroup of international experts. Twenty-four samples from patients with suspected idiopathic inflammatory myopathy (IIM) were randomly selected, providing sections that … [Read more]
Routine cerebrospinal fluid cytology reveals unique inclusions in macrophages during treatment with nusinersen
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder characterized by degeneration of spinal motor neurons leading to muscular weakness. The antisense oligonucleotide nusinersen was approved for the treatment of patients with 5q-associated SMA. Treatment must be repeatedly administered intrathecally by lumbar puncture. So far, data regarding cerebrospinal fluid (CSF) parameters are sparse and … [Read more]
Ataluren use in patients with nonsense mutation DMD: patient demographics and characteristics from the STRIDE Registry
Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (DMD) in clinical practice (NCT02369731). Here, the authors describe the initial demographic characteristics of the registry population. Patients will be followed up from enrollment for ≥5 … [Read more]
A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene
Neuromuscular disorders are often caused by heterogeneous mutations in large, structurally complex genes. Targeting compensatory modifier genes could be beneficial to improve disease phenotypes. Here the authors report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice. MDC1A … [Read more]
Analysis of the functional capacity outcome measures for DM1
Defining clinically relevant outcome measures for myotonic dystrophy type 1 (DM1) that can be valid and feasible for different phenotypes has proven problematic. The Outcome Measures for Myotonic Dystrophy (OMMYD) group proposed a battery of functional outcomes: 6-minute walk test, 30 seconds sit and stand test, timed 10 m walk test, timed 10 m walk/run … [Read more]
