Background: Dilated cardiomyopathy (DCM) is familial in about 20-35% of patients. The most frequently encountered mutations associated with DCM are found in LMNA.
Aim: To define the frequency of LMNA mutations in a series of consecutive DCM patients and to evaluate the phenotype of mutation carriers.
Methods: We screened the 12 exons of LMNA in a series of 61 Polish patients with DCM diagnosed angiographically, as well as in two DCM families.
Results: Two mutations were detected in 5 mutation carriers (D192G in one proband and Y481Stop in one proband and 3 of his offspring), which represents 3.3% (2/61) of the DCM patients. These mutations were absent from 100 controls. The D192G mutation was found in a 26-year-old patient with mild DCM and heart failure leading to death within two years after onset of symptoms. Mild conduction disease was also present. Ultrastructural analysis of the endomyocardial biopsy showed a striking alteration of nuclear morphology. This finding can explain nuclear fragility and is in agreement with the pathophysiological mechanical hypothesis of LMNA mutations. All four Y481Stop mutation-carriers were affected. Three phenotypes were found: in the proband, cardiac dysrhythmia and pacemaker requirement preceded DCM leading to heart transplantation; the proband's 13-year old daughter had conduction disease (2nd degree A-V block) with subtle skeletal muscle involvement documented by immunofluorescence study; ventricular arrhythmia was detected in the proband's son at the age of 11 and in the proband's daughter at the age of 18. Serum creatine kinase was normal in all mutation carriers.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Role of lamins in cellular physiology and cancer.
Adv Protein Chem Struct Biol
January 2025
Department of Medical Oncology (Lab), Dr. B.R. Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India. Electronic address:
Lamins, which are crucial type V intermediate filament proteins found in the nuclear lamina, are essential for maintaining the stability and function of the nucleus in higher vertebrates. They are classified into A- and B-types, and their distinct expression patterns contribute to cellular survival, development, and functionality. Lamins emerged during the transition from open to closed mitosis, with their complexity increasing alongside organism evolution.
View Article and Find Full Text PDFThe anti-senescence effect of D-β-hydroxybutyrate in Hutchinson-Gilford progeria syndrome involves progerin clearance by the activation of the AMPK-mTOR-autophagy pathway.
Geroscience
January 2025
Department of Neuropathology, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), 04510, Mexico City, Mexico.
D-β-hydroxybutyrate, BHB, has been previously proposed as an anti-senescent agent in vitro and in vivo in several tissues including vascular smooth muscle. Moreover, BHB derivatives as ketone esters alleviate heart failure. Here, we provide evidence of the potential therapeutic effect of BHB on Hutchinson-Gilford progeria syndrome (HGPS), a rare condition characterized by premature aging and heart failure, caused by the presence of progerin, the aberrant protein derived from LMNA/C gene c.
View Article and Find Full Text PDFCongenital muscular dystrophies and myopathies: the leading cause of genetic muscular disorders in eleven Chinese families.
BMC Musculoskelet Disord
January 2025
Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, China.
Background: Congenital muscular dystrophies (CMDs) and myopathies (CMYOs) are a clinically and genetically heterogeneous group of neuromuscular disorders that share common features, such as muscle weakness, hypotonia, characteristic changes on muscle biopsy and motor retardation. In this study, we recruited eleven families with early-onset neuromuscular disorders in China, aimed to clarify the underlying genetic etiology.
Methods: Essential clinical tests, such as biomedical examination, electromyography and muscle biopsy, were applied to evaluate patient phenotypes.
Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of function mutation.
Nucleus
December 2025
Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
Over the past 25 years, nuclear envelope (NE) perturbations have been reported in various experimental models with mutations in the gene. Although the hypothesis that NE perturbations from mutations are a fundamental feature of striated muscle damage has garnered wide acceptance, the molecular sequalae provoked by the NE damage and how they underlie disease pathogenesis such as cardiomyopathy ( cardiomyopathy) remain poorly understood. We recently shed light on one such consequence, by employing a cardiomyocyte-specific deletion in the adult heart.
View Article and Find Full Text PDFImaging-Based Molecular Interaction Between Src and Lamin A/C Mechanosensitive Proteins in the Nucleus of Laminopathic Cells.
Int J Mol Sci
December 2024
Bone Pathophysiology Research Unit, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Laminopathies represent a wide range of genetic disorders caused by mutations in gene-encoding proteins of the nuclear lamina. Altered nuclear mechanics have been associated with laminopathies, given the key role of nuclear lamins as mechanosensitive proteins involved in the mechanotransduction process. To shed light on the nuclear partners cooperating with altered lamins, we focused on Src tyrosine kinase, known to phosphorylate proteins of the nuclear lamina.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!