Article

Limb-girdle muscular dystrophy in the United States.

University of Iowa, Iowa City, 52242, USA.
Journal of Neuropathology and Experimental Neurology (Impact Factor: 4.37). 11/2006; 65(10):995-1003. DOI: 10.1097/01.jnen.0000235854.77716.6c
Source: PubMed

ABSTRACT Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7 autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To determine the distribution of subtypes among patients in the United States, 6 medical centers evaluated patients with a referral diagnosis of LGMD. Muscle biopsies provided histopathology and immunodiagnostic testing, and their protein abnormalities along with clinical parameters directed mutation screening. The diagnosis in 23 patients was a disorder other than LGMD. Of the remaining 289 unrelated patients, 266 had muscle biopsies sufficient for complete microscopic evaluation; 121 also underwent Western blotting. From this combined evaluation, the distribution of immunophenotypes is 12% calpainopathy, 18% dysferlinopathy, 15% sarcoglycanopathy, 15% dystroglycanopathy, and 1.5% caveolinopathy. Genotypes distributed among 2 dominant and 7 recessive subtypes have been determined for 83 patients. This study of a large racially and ethnically diverse population of patients with LGMD indicates that establishing a putative subtype is possible more than half the time using available diagnostic testing. An efficient approach to genotypic diagnosis is muscle biopsy immunophenotyping followed by directed mutational analysis. The most common LGMDs in the United States are calpainopathies, dysferlinopathies, sarcoglycanopathies, and dystroglycanopathies.

0 Followers
 · 
235 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of disorders, which has led to certain investigators disputing its rationality. The mutual feature of LGMD is limb-girdle affection. Magnetic resonance imaging (MRI), perioral skin biopsies, blood-based assays, reverse‑protein arrays, proteomic analyses, gene chips and next generation sequencing are the leading diagnostic techniques for LGMD and gene, cell and pharmaceutical treatments are the mainstay therapies for these genetic disorders. Recently, more highlights have been shed on disease biomarkers to follow up disease progression and to monitor therapeutic responsiveness in future trials. In this study, we review LGMD from a variety of aspects, paying specific attention to newly evolving research, with the purpose of bringing this information into the clinical setting to aid the development of novel therapeutic strategies for this hereditary disease. In conclusion, substantial progress in our ability to diagnose and treat LGMD has been made in recent decades, however enhancing our understanding of the detailed pathophysiology of LGMD may enhance our ability to improve disease outcome in subsequent years.
    Molecular Medicine Reports 03/2014; 9(5). DOI:10.3892/mmr.2014.2048 · 1.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Gene therapy for the muscular dystrophies has evolved as a promising treatment for this progressive group of disorders. Although corticosteroids and/or supportive treatments remain the standard of care for Duchenne muscular dystrophy, loss of ambulation, respiratory failure, and compromised cardiac function is the inevitable outcome. Recent developments in genetically mediated therapies have allowed for personalized treatments that strategically target individual muscular dystrophy subtypes based on disease pathomechanism and phenotype. In this review, we highlight the therapeutic progress with emphasis on evolving preclinical data and our own experience in completed clinical trials and others currently underway. We also discuss the lessons we have learned along the way and the strategies developed to overcome limitations and obstacles in this field. Copyright © 2014 Elsevier Inc. All rights reserved.
    Pediatric Neurology 11/2014; 51(5):607-618. DOI:10.1016/j.pediatrneurol.2014.08.002 · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The relative frequencies of different subtypes of limb-girdle muscular dystrophies vary widely among different populations. We estimated the percentage of limb-girdle muscular dystrophy subtypes in Chinese people based on 68 patients with limb-girdle muscular dystrophy from the Myology Clinic, Neurology Department, First Hospital of Jilin University, China. A diagnosis of calpainopathy was made in 12 cases (17%), and dysferlin deficiency in 10 cases (15%). Two biopsies revealed α-sarcoglycan deficiency (3%), and two others revealed a lack of caveolin-3 (3%). A diagnosis of unclassified limb-girdle muscular dystrophy was made in the remaining patients (62%). The appearances of calpain 3- and dysferlin-deficient biopsies were similar, though rimmed vacuoles were unique to dysferlinopathy, while inflammatory infiltrates were present in both these limb-girdle muscular dystrophy type 2D biopsies. Macrophages were detected in seven dysferlinopathy biopsies. The results of this study suggest that the distribution of limb-girdle muscular dystrophy subtypes in the Han Chinese population is similar to that reported in the West. The less necrotic, regenerating and inflammatory appearance of limb-girdle muscular dystrophy type 2A, but with more lobulated fibers, supports the idea that calpainopathy is a less active, but more chronic disease than dysferlinopathy. Unusual features indicated an extended limb-girdle muscular dystrophy disease spectrum. The use of acid phosphatase stain should be considered in suspected dysferlinopathies. To the best of our knowledge, this is the first report to define the relative proportions of the various forms of limb-girdle muscular dystrophy in China, based on protein testing.
    Neural Regeneration Research 07/2013; 8(20):1907-18. DOI:10.3969/j.issn.1673-5374.2013.20.010 · 0.23 Impact Factor

Full-text (2 Sources)

Download
202 Downloads
Available from
May 21, 2014