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Context: There is no current standard among myopathologists for reporting muscle biopsy findings. The National Institute of Neurological Disorders and Stroke has recently launched a common data element (CDE) project to standardize neuromuscular data collected in clinical reports and to facilitate their use in research., Objective: To develop a more-uniform, prospective reporting tool for muscle biopsies, incorporating the elements identified by the CDE project, in an effort to improve reporting and educational resources., Design: The variation in current biopsy reporting practice was evaluated through a study of 51 muscle biopsy reports from self-reported diagnoses of genetically confirmed or undiagnosed muscle disease from the Congenital Muscle Disease International Registry. Two reviewers independently extracted data from deidentified reports and entered them into the revised CDE format to identify what was missing and whether or not information provided on the revised CDE report (complete/incomplete) could be successfully interpreted by a neuropathologist., Results: Analysis of the data highlighted showed (1) inconsistent reporting of key clinical features from referring physicians, and (2) considerable variability in the reporting of pertinent positive and negative histologic findings by pathologists., Conclusions: We propose a format for muscle-biopsy reporting that includes the elements in the CDE checklist and a brief narrative comment that interprets the data in support of a final interpretation. Such a format standardizes cataloging of pathologic findings across the spectrum of muscle diseases and serves emerging clinical care and research needs with the expansion of genetic-testing therapeutic trials.

The congenital muscular dystrophies (CMDs) comprise a heterogeneous group of heritable muscle disorders with often difficult to interpret muscle pathology, making them challenging to diagnose. Serial Sanger sequencing of suspected CMD genes, while the current molecular diagnostic method of choice, can be slow and expensive. A comprehensive panel test for simultaneous screening of mutations in all known CMD-associated genes would be a more effective diagnostic strategy. Thus, the CMDs are a model disorder group for development and validation of next-generation sequencing (NGS) strategies for diagnostic and clinical care applications. Using a highly multiplexed PCR-based target enrichment method (RainDance) in conjunction with NGS, we performed mutation detection in all CMD genes of 26 samples and compared the results with Sanger sequencing. The RainDance NGS panel showed great consistency in coverage depth, on-target efficiency, versatility of mutation detection, and genotype concordance with Sanger sequencing, demonstrating the test's appropriateness for clinical use. Compared to single tests, a higher diagnostic yield was observed by panel implementation. The panel's limitation is the amplification failure of select gene-specific exons which require Sanger sequencing for test completion. Successful validation and application of the CMD NGS panel to improve the diagnostic yield in a clinical laboratory was shown. [ABSTRACT FROM AUTHOR]

The article examines the association between nonsense mutations and muscular dystrophy including Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD). A survey is conducted and the result identified 243 nonsense mutations in the DMD gene, and in 210 a definitive phenotypes could be established. In patients where nonsense mutations were found, the reading frame predicted by exons were analyzed and revealed that by inducing exon definition skipping, the exonic point mutations could be used in determining phenotypes.

Congenital muscular dystrophies are a group of rare neuromuscular disorders with a wide spectrum of clinical phenotypes. Recent advances in understanding the molecular pathogenesis of congenital muscular dystrophy have enabled better diagnosis. However, medical care for patients with congenital muscular dystrophy remains very diverse. Advances in many areas of medical technology have not been adopted in clinical practice. The International Standard of Care Committee for Congenital Muscular Dystrophy was established to identify current care issues, review literature for evidence-based practice, and achieve consensus on care recommendations in 7 areas: diagnosis, neurology, pulmonology, orthopedics/rehabilitation, gastroenterology/ nutrition/speech/oral care, cardiology, and palliative care. To achieve consensus on the care recommendations, 2 separate online surveys were conducted to poll opinions from experts in the field and from congenital muscular dystrophy families. The final consensus was achieved in a 3-day workshop conducted in Brussels, Belgium, in November 2009. This consensus statement describes the care recommendations from this committee. [ABSTRACT FROM PUBLISHER]

During the past decade, outstanding progress in the areas of congenital and limb-girdle muscular dystrophies has led to staggering clinical and genetic complexity. With the identification of an increasing number of genetic defects, individual entities have come into sharper focus and new pathogenic mechanisms for muscular dystrophies, like defects of posttranslational O-linked glycosylation, have been discovered. At the same time, this progress blurs the traditional boundaries between the categories of congenital and limb-girdle muscular dystrophies, as well as between limb-girdle muscular dystrophies and other clinical entities, as mutations in genes such as fukutin-related protein, dysferlin, caveolin-3 and lamin A/C can cause a striking variety of phenotypes. We reviewed the different groups of proteins currently recognized as being involved in congenital and limb-girdle muscular dystrophies, associated them with the clinical phenotypes, and determined some clinical and molecular clues that are helpful in the diagnostic approach to these patients. [ABSTRACT FROM AUTHOR]