The non-muscle ADF/cofilin-1 controls sarcomeric actin filament integrity and force production in striated muscle laminopathies.

Cofilins are important for the regulation of the actin cytoskeleton, sarcomere organization, and force production. The role of cofilin-1, the non-muscle-specific isoform, in muscle function remains unclear. Mutations in LMNA encoding A-type lamins, intermediate filament proteins of the nuclear envelope, cause autosomal Emery-Dreifuss muscular dystrophy (EDMD).

Generation of one control and four iPSCs clones from patients with Emery-Dreifuss muscular dystrophy type 1.

Emery-Dreifuss muscular dystrophy type 1 (EDMD1) is a rare genetic disease caused by mutations in the EMD gene coding for a nuclear envelope protein emerin. We generated and characterized induced pluripotent stem cells (iPSCs) from two EDMD1 patients bearing a mutation c.del153C and from one healthy donor.

SARS-CoV-2 Infection and Emery-Dreifuss Syndrome in a Young Patient with a Family History of Dilated Cardiomyopathy.

Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetic disease that affects the musculoskeletal system, including the heart, causing rhythm disorders and cardiomyopathy, sometimes requiring an implantable cardioverter-defibrillator (ICD) or heart transplantation due to severe heart damage. The case described herein concerns a 16-year-old girl, with grade II obesity, without other known pathological antecedents or cardiac pathology diagnosis given an annual history of cardiological investigations. She was admitted to the Infectious Diseases Department with SARS-CoV-2 virus infection.

Adenine base editing to treat progeria syndrome and extend the lifespan.

Hutchinson-Gilford progeria syndrome (HGPS) is an exceedingly rare and hitherto incurable and fatal disease marked by accelerated aging simultaneously affecting a number of organs. Most cases of HGPS are caused by a single copy of a specific single-nucleotide mutation, c.C1824T, in the (lamin A) gene.

Emerin Represses STAT3 Signaling through Nuclear Membrane-Based Spatial Control.

Emerin is the inner nuclear membrane protein involved in maintaining the mechanical integrity of the nuclear membrane. Mutations in EMD encoding emerin cause Emery-Dreifuss muscular dystrophy (EDMD). Evidence is accumulating that emerin regulation of specific gene expression is associated with this disease, but the exact function of emerin has not been fully elucidated.

At the nuclear envelope of bone mechanobiology.

The nuclear envelope and nucleoskeleton are emerging as signaling centers that regulate how physical information from the extracellular matrix is biochemically transduced into the nucleus, affecting chromatin and controlling cell function. Bone is a mechanically driven tissue that relies on physical information to maintain its physiological function and structure. Disorder that present with musculoskeletal and cardiac symptoms, such as Emery-Dreifuss muscular dystrophies and progeria, correlate with mutations in nuclear envelope proteins including Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, Lamin A/C, and emerin.

Case Reports: Emery-Dreifuss Muscular Dystrophy Presenting as a Heart Rhythm Disorders in Children.

Emery-Dreifuss muscular dystrophy (EDMD) is inherited muscle dystrophy often accompanied by cardiac abnormalities in the form of supraventricular arrhythmias, conduction defects and sinus node dysfunction. Cardiac phenotype typically arises years after skeletal muscle presentation, though, could be severe and life-threatening. The defined clinical manifestation with joint contractures, progressive muscle weakness and atrophy, as well as cardiac symptoms are observed by the third decade of life.

Skeletal and Cardiac Muscle Disorders Caused by Mutations in Genes Encoding Intermediate Filament Proteins.

Intermediate filaments are major components of the cytoskeleton. Desmin and synemin, cytoplasmic intermediate filament proteins and A-type lamins, nuclear intermediate filament proteins, play key roles in skeletal and cardiac muscle. Desmin, encoded by the gene (OMIM *125660) and A-type lamins by the gene (OMIM *150330), have been involved in striated muscle disorders.

Role of in the Emery-Dreifuss Muscular Dystrophy Cardiac Phenotype.

The locus is one of the most studied tumor suppressor loci in the context of several cancer types. However, in the last years, its expression has also been linked to terminal differentiation and the activation of the senescence program in different cellular subtypes. Knock-out (KO) of the entire locus enhances the capability of stem cells to proliferate in some tissues and respond to severe physiological and non-physiological damages in different organs, including the heart.

Cardiac Arrhythmias in Muscular Dystrophies Associated with Emerinopathy and Laminopathy: A Cohort Study.

Introduction: Cardiac involvement in patients with muscular dystrophy associated with Lamin A/C mutations () is characterized by atrioventricular conduction abnormalities and life-threatening cardiac arrhythmias. Little is known about cardiac involvement in patients with emerin mutation (). The aim of our study was to describe and compare the prevalence and time distribution of cardiac arrhythmias at extended follow-up.

A splicing LMNA mutation causing laminopathies accompanied by aortic valve malformation.

Background: Laminopathies caused by LMNA gene mutations are characterized by different clinical manifestations. Among them, cardiac involvement is one of the most severe phenotypes.

Case Presentation: A 30-year-old man visited the hospital because of palpitations, shortness of breath, and fatigue.

Echocardiographic Features of Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy.

Background: Emery-Dreifuss muscular dystrophy (EDMD) is a very rare type of muscular dystrophy characterized by musculoskeletal abnormalities accompanied by cardiac defects. Two most common genetic subtypes are EDMD1 due to and EDMD2 caused by LMNA gene mutations. The aim of the study was to characterize and compare the cardiac morphology and function in the two main genetic subgroups of EDMD with the use of echocardiography.

Cardiac MR Imaging of Muscular Dystrophies.

Muscular dystrophies (MDs) are a group of inherited disorders caused by mutations that interfere with muscular structure, contraction, or relaxation. As the cardiac sarcomeric unit shares multiple proteins with the skeletal muscle unit, the heart is affected in several MDs, sometimes without apparent musculoskeletal involvement. Early detection of MD-related cardiomyopathy is crucial as timely initiation of cardioprotective therapy can slow adverse cardiac remodeling.

The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization.

Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism.

Staged Management of Cervicothoracic Lordosis and Scoliosis in an Emery-Dreifuss VI Muscular Dystrophy Patient: A Case Report.

Case: We report the case of an 18-year-old man with extreme cervicothoracic lordosis and a progressive scoliosis secondary to Emery-Dreifuss Type VI muscular dystrophy. In a staged fashion, the patient underwent posterior cervical muscle release, halo-gravity traction, and posterior instrumented spinal fusion from C3-L4 with multiple posterior column osteotomies. The patient was followed over 2 years postoperatively with restoration of normal spinal alignment in both the coronal and sagittal profiles.

Lamin-Related Congenital Muscular Dystrophy Alters Mechanical Signaling and Skeletal Muscle Growth.

Laminopathies are a clinically heterogeneous group of disorders caused by mutations in the gene, which encodes the nuclear envelope proteins lamins A and C. The most frequent diseases associated with mutations are characterized by skeletal and cardiac involvement, and include autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B, and -related congenital muscular dystrophy (-CMD). Although the exact pathophysiological mechanisms responsible for -CMD are not yet understood, severe contracture and muscle atrophy suggest that mutations may impair skeletal muscle growth.

Ryanodine receptor remodeling in cardiomyopathy and muscular dystrophy caused by lamin A/C gene mutation.

Mutations in the lamin A/C gene (LMNA), which encodes A-type lamins, cause several diseases called laminopathies, the most common of which is dilated cardiomyopathy with muscular dystrophy. The role of Ca2+ regulation in these diseases remain poorly understood. We now show biochemical remodeling of the ryanodine receptor (RyR)/intracellular Ca2+ release channel in heart samples from human subjects with LMNA mutations, including protein kinase A-catalyzed phosphorylation, oxidation and depletion of the stabilizing subunit calstabin.

Human VAPome Analysis Reveals MOSPD1 and MOSPD3 as Membrane Contact Site Proteins Interacting with FFAT-Related FFNT Motifs.

Membrane contact sites (MCS) are intracellular regions where two organelles come closer to exchange information and material. The majority of the endoplasmic reticulum (ER) MCS are attributed to the ER-localized tether proteins VAPA, VAPB, and MOSPD2. These recruit other proteins to the ER by interacting with their FFAT motifs.

Clinical and Genomic Evaluation of 207 Genetic Myopathies in the Indian Subcontinent.

Inherited myopathies comprise more than 200 different individually rare disease-subtypes, but when combined together they have a high prevalence of 1 in 6,000 individuals across the world. Our goal was to determine for the first time the clinical- and gene-variant spectrum of genetic myopathies in a substantial cohort study of the Indian subcontinent. In this cohort study, we performed the first large clinical exome sequencing (ES) study with phenotype correlation on 207 clinically well-characterized inherited myopathy-suspected patients from the Indian subcontinent with diverse ethnicities.

Relationship between infrared skin radiation and functional tests in patients affected by Emery-Dreifuss muscular dystrophy: Part 2.

This study represents a second part of a recently published study about a new form of evaluation and development of rare genetic neurodegenerative diseases. The objective is to provide a more global vision of thermography with respect to the Emery-Dreifuss pathology, through the analysis of the data collection carried out for one year. The basic hypothesis is that thermography could become a valid tool for the diagnosis and follow-up of this pathology because is a very specific tool for registering temperature changes produced by a constant degenerative evolution of this muscular dystrophy.

Need for NAD: Focus on Striated Muscle Laminopathies.

Laminopathies are a heterogeneous group of rare diseases caused by genetic mutations in the gene, encoding A-type lamins. A-type lamins are nuclear envelope proteins which associate with B-type lamins to form the nuclear lamina, a meshwork underlying the inner nuclear envelope of differentiated cells. The laminopathies include lipodystrophies, progeroid phenotypes and striated muscle diseases.

Novel FHL1 mutation variant identified in a patient with nonobstructive hypertrophic cardiomyopathy and myopathy - a case report.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic disorder mostly caused by sarcomeric gene mutations, but almost 10% of cases are attributed to inherited metabolic and neuromuscular disorders. First described in 2008 in an American-Italian family with scapuloperoneal myopathy, FHL1 gene encodes four-and-a-half LIM domains 1 proteins which are involved in sarcomere formation, assembly and biomechanical stress sensing both in cardiac and skeletal muscle, and its mutations are responsible for a large spectrum of neuromuscular disorders (mostly myopathies) and cardiac disease, represented by HCM, either isolated, or in conjunction with neurologic and skeletal muscle impairment. We thereby report a novel mutation variant in FHL1 structure, associated with HCM and type 6 Emery-Dreifuss muscular dystrophy (EDMD).