Article

Laminopathies: multisystem dystrophy syndromes.

Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, 75390-9052, USA.
Molecular Genetics and Metabolism (Impact Factor: 2.83). 05/2006; 87(4):289-302. DOI:10.1016/j.ymgme.2005.10.018
Source: PubMed

ABSTRACT Laminopathies are a heterogeneous group of genetic disorders due to abnormalities in type A lamins and can manifest varied clinical features affecting many organs including the skeletal and cardiac muscle, adipose tissue, nervous system, cutaneous tissue, and bone. Mutations in the gene encoding lamins A and C (LMNA) cause primary laminopathies, including various types of lipodystrophies, muscular dystrophies and progeroid syndromes, mandibuloacral dysplasia, dilated cardiomyopathies, and restrictive dermopathy. The secondary laminopathies are due to mutations in ZMPSTE24 gene which encodes for a zinc metalloproteinase involved in processing of prelamin A into mature lamin A and cause mandibuloacral dysplasia and restrictive dermopathy. Skin fibroblast cells from many patients with laminopathies show a range of abnormal nuclear morphology including bleb formation, honeycombing, and presence of multi-lobulated nuclei. The mechanisms by which mutations in LMNA gene cause multisystem dystrophy are an active area of current investigation. Further studies are needed to understand the underlying mechanisms of marked pleiotropy in laminopathies.

0 0
 · 
0 Bookmarks
 · 
77 Views
  • [show abstract] [hide abstract]
    ABSTRACT: LMNA gene mutations are associated with cardiac and skeletal muscle alterations. A cohort of 21 mutated individuals was assessed with clinical and instrumental investigations over the years. The median observation period was 6 years. Cardiac compromise was detected in 16 patients. Bradyarrhythmias were the most frequent manifestations, followed by supraventricular arrhythmias. Two individuals suffered from nonsustained and 1 from sustained ventricular tachyarrhythmias. Dilated cardiomyopathy was detected in 3 patients. Evaluation of the frequencies of the clinical expressions showed a high probability of suffering from analogue heart compromise in study subjects bearing the same LMNA gene mutation. Cardiac involvement represents a very common phenotypic expression of LMNA gene mutation. Subjects sharing common genetic background seem to suffer from analogue pattern of cardiac manifestation.
    Muscle & Nerve 08/2012; 46(2):187-92. · 2.31 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Musculoskeletal aging is detrimental to multiple bodily functions and starts early, probably in the fourth decade of an individual's life. Sarcopenia is a health problem that is expected to only increase as a greater portion of the population lives longer; prevalence of the related musculoskeletal diseases is similarly expected to increase. Unraveling the biological and biomechanical associations and molecular mechanisms underlying these diseases represents a formidable challenge. There are two major problems making disentangling the biological complexity of musculoskeletal aging difficult: (a) it is a systemic, rather than "compartmental," problem, which should be approached accordingly, and (b) the aging per se is neither well defined nor reliably measurable. A unique challenge of studying any age-related condition is a need of distinguishing between the "norm" and "pathology," which are interwoven throughout the aging organism. We argue that detecting genes with pleiotropic functions in musculoskeletal aging is needed to provide insights into the potential biological mechanisms underlying inter-individual differences insusceptibility to the musculoskeletal diseases. However, exploring pleiotropic relationships among the system's components is challenging both methodologically and conceptually. We aimed to focus on genetic aspects of the cross-talk between muscle and its "neighboring" tissues and organs (tendon, bone, and cartilage), and to explore the role of genetics to find the new molecular links between skeletal muscle and other parts of the "musculoskeleton." Identification of significant genetic variants underlying the musculoskeletal system's aging is now possible more than ever due to the currently available advanced genomic technologies. In summary, a "holistic" genetic approach is needed to study the systems's normal functioning and the disease predisposition in order to improve musculoskeletal health.
    Frontiers in Physiology 01/2012; 3:303.
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Hutchinson-Gilford Progeria Syndrome and Werner syndrome, also known as childhood- and adulthood-progeria, respectively, represent two of the best characterized human progeroid diseases with clinical features mimicking physiological aging at an early age. The discovery of their genetic basis has led to the identification of several gene mutations leading to a spectrum of progeroid phenotypes ranging from moderate and mild-severe to very aggressive forms. In parallel, the creation of disease registers and databases provided available data for the design of relatively large-scale epidemiological studies, thereby allowing a better understanding of the nature and frequency of the premature aging-associated signs and symptoms. The aim of this article is to review the most recent findings concerning the epidemiology of premature aging disorders, their genetic basis, and the most recent reports on the frequency of associated diseases.
    Clinical Interventions in Aging 01/2013; 8:1023-1032. · 2.65 Impact Factor

Katherine N Jacob