Clinical and imaging spectrum of non-congenital dominant ACTN2 myopathy.

Background: Alpha-actinin-2, a protein with high expression in cardiac and skeletal muscle, is located in the Z-disc and plays a key role in sarcomere stability. Mutations in ACTN2 have been associated with both hypertrophic and dilated cardiomyopathy and, more recently, with skeletal myopathy.

Methods: Genetic, clinical, and muscle imaging data were collected from 37 patients with an autosomal dominant ACTN2 myopathy belonging to 11 families from Spain and Belgium.

A founder variant in the RYR1 gene is associated with hyperCKemia, myalgia and muscle cramps.

Background And Purpose: Pathogenic variants in the RYR1 gene have been associated with a variety of conditions, ranging from congenital myopathy to adult manifestations. Our aim was to characterize the p.Leu2286Val variant in 17 Basque patients, to accurately determine its correlation with clinical features and to explore the possible founder effect of the variant.

Biallelic variants in SNUPN cause a limb girdle muscular dystrophy with myofibrillar-like features.

Alterations in RNA-splicing are a molecular hallmark of several neurological diseases, including muscular dystrophies, where mutations in genes involved in RNA metabolism or characterized by alterations in RNA splicing have been described. Here, we present five patients from two unrelated families with a limb-girdle muscular dystrophy (LGMD) phenotype carrying a biallelic variant in SNUPN gene. Snurportin-1, the protein encoded by SNUPN, plays an important role in the nuclear transport of small nuclear ribonucleoproteins (snRNPs), essential components of the spliceosome.

Analysis of muscle magnetic resonance imaging of a large cohort of patient with VCP-mediated disease reveals characteristic features useful for diagnosis.

Background: The diagnosis of patients with mutations in the VCP gene can be complicated due to their broad phenotypic spectrum including myopathy, motor neuron disease and peripheral neuropathy. Muscle MRI guides the diagnosis in neuromuscular diseases (NMDs); however, comprehensive muscle MRI features for VCP patients have not been reported so far.

Methods: We collected muscle MRIs of 80 of the 255 patients who participated in the "VCP International Study" and reviewed the T1-weighted (T1w) and short tau inversion recovery (STIR) sequences.

Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1).

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the 3' untranslated region of the dystrophia myotonica protein kinase gene. AKT dephosphorylation and autophagy are associated with DM1. Autophagy has been widely studied in DM1, although the endocytic pathway has not.

Senescence plays a role in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1; MIM #160900) is an autosomal dominant disorder, clinically characterized by progressive muscular weakness and multisystem degeneration. The broad phenotypes observed in patients with DM1 resemble the appearance of an accelerated aging process. However, the molecular mechanisms underlying these phenotypes remain largely unknown.

Three-year quantitative magnetic resonance imaging and phosphorus magnetic resonance spectroscopy study in lower limb muscle in dysferlinopathy.

Background: Natural history studies in neuromuscular disorders are vital to understand the disease evolution and to find sensitive outcome measures. We performed a longitudinal assessment of quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy ( P MRS) outcome measures and evaluated their relationship with function in lower limb skeletal muscle of dysferlinopathy patients.

Methods: Quantitative MRI/ P MRS data were obtained at 3 T in two different sites in 54 patients and 12 controls, at baseline, and three annual follow-up visits.

Muscle MRI characteristic pattern for late-onset TK2 deficiency diagnosis.

Background And Objective: TK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development.

Cardiac and pulmonary findings in dysferlinopathy: A 3-year, longitudinal study.

Introduction/aims: There is debate about whether and to what extent either respiratory or cardiac dysfunction occurs in patients with dysferlinopathy. This study aimed to establish definitively whether dysfunction in either system is part of the dysferlinopathy phenotype.

Methods: As part of the Jain Foundation's International Clinical Outcome Study (COS) for dysferlinopathy, objective measures of respiratory and cardiac function were collected twice, with a 3-y interval between tests, in 188 genetically confirmed patients aged 11-86 y (53% female).

Miyoshi myopathy and limb girdle muscular dystrophy R2 are the same disease.

This study aims to determine clinically relevant phenotypic differences between the two most common phenotypic classifications in dysferlinopathy, limb girdle muscular dystrophy R2 (LGMDR2) and Miyoshi myopathy (MMD1). LGMDR2 and MMD1 are reported to involve different muscles, with LGMDR2 showing predominant limb girdle weakness and MMD1 showing predominant distal lower limb weakness. We used heatmaps, regression analysis and principle component analysis of functional and Magnetic Resonance Imaging data to perform a cross-sectional review of the pattern of muscle involvement in 168 patients from the Jain Foundation's international Clinical Outcomes Study for Dysferlinopathy.

Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity on T1W Magnetic Resonance Imaging in Adults With Dysferlinopathy.

Practice of sports during childhood or adolescence correlates with an earlier onset and more rapidly progressing phenotype in dysferlinopathies. To determine if this correlation relates to greater muscle pathology that persists into adulthood, we investigated the effect of exercise on the degree of muscle fatty replacement measured using muscle MRI. We reviewed pelvic, thigh and leg T1W MRI scans from 160 patients with genetically confirmed dysferlinopathy from the Jain Foundation International clinical outcomes study in dysferlinopathy.

Myotonic Dystrophy type 1 cells display impaired metabolism and mitochondrial dysfunction that are reversed by metformin.

Myotonic dystrophy type 1 (DM1; MIM #160900) is an autosomal dominant disorder, clinically characterized by progressive muscular weakness and multisystem degeneration. The broad phenotypes observed in patients with DM1 resemble the appearance of a multisystem accelerated aging process. However, the molecular mechanisms underlying these phenotypes remain largely unknown.

A comprehensive serum lipidome profiling of amyotrophic lateral sclerosis.

: To perform a comprehensive lipid profiling to evaluate potential lipid metabolic differences between patients with amyotrophic lateral sclerosis (ALS) and controls, and to provide a more profound understanding of the metabolic abnormalities in ALS. : Twenty patients with ALS and 20 healthy controls were enrolled in a cross-sectional study. Untargeted lipidomics profiling in fasting serum samples were performed by optimized UPLC-MS platforms for broad lipidome coverage.

Clinical and therapeutic features of myasthenia gravis in adults based on age at onset.

Objective: To describe the characteristics of patients with very-late-onset myasthenia gravis (MG).

Methods: This observational cross-sectional multicenter study was based on information in the neurologist-driven Spanish Registry of Neuromuscular Diseases (NMD-ES). All patients were >18 years of age at onset of MG and onset occurred between 2000 and 2016 in all cases.

Leukocyte telomere length in patients with myotonic dystrophy type I: a pilot study.

Myotonic dystrophy type I (DM1) is an autosomal dominant disease of which clinical manifestations resemble premature aging. We evaluated the contribution of telomere length in pathogenesis in 361 DM1 patients (12 with serial measurements) and 223 unaffected relative controls using qPCR assay. While no differences in baseline leukocyte relative telomere length (RTL) was noted, the data suggested an accelerated RTL attrition in DM1 (discovery cohort: T/S change/year = -0.

MYO-MRI diagnostic protocols in genetic myopathies.

Whole-body magnetic resonance imaging has emerged as a useful imaging tool in diagnosing and characterizing the progression of myopathies and muscular dystrophies. Whole-body MRI indications and diagnostic efficacy are becoming better defined with the increasing number of cases, publications and discussions within multidisciplinary working groups. Advanced Whole-body MRI protocols are rapid, lower cost, and well-tolerated by patients.