F Muntoni

..This study, together with previous reports, suggests that some patients with DC have a dystrophinopathy that can be diagnosed using a combination of biochemical and genetic analyses...

..Furthermore, digenic inheritance may well contribute to the clinical severity of many other neuromuscular disorders...

..Mutations of the LMNA gene, encoding the nuclear envelope proteins lamins A and C, have been associated with 7 distinct pathologic conditions...

..This article provides an overview of the clinical, biochemical and genetic advances that have been made over the last year in this field...

....

....

..Disrupted glycosylation of alpha-dystroglycan results in a loss of these interactions, giving rise to both progressive muscle degeneration and abnormal neuronal migration in the brain...

..Here, we focus on current understanding of the genotype-phenotype relation for mutations in the dystrophin gene and their implications for gene functions...

..This article is focused on practical clinical suggestions on when to suspect and how to investigate patients with a cardiomyopathy secondary to neuromuscular disorders...

..This review focuses on three areas in which experimental clinical studies are in progress...

..We also examine the possibility that some rare human conditions associated with abnormal muscle formation may be due to genetic defects in one of the myogenic regulatory genes...

..External ophthalmoplegia is an additional finding in a subset of patients with MmD...

..The secondary reduction in laminin-alpha2 chain in these families suggests that the primary genetic defect resides in a gene coding for a protein involved in basal lamina assembly...

..The spectrum of LGMD2I phenotypes ranged from infants with an early presentation and a Duchenne-like disease course including cardiomyopathy, to milder phenotypes compatible with a favourable long-term outcome...

..To describe the course, complications, and prognosis of Ullrich congenital muscular dystrophy (UCMD), with special reference to life-changing events, including loss of ambulation, respiratory insufficiency, and death...

..The fourth case had a mild and late-onset LGMD1B phenotype. Our cases further expand the clinical spectrum associated with mutations in the LMNA gene and provide new evidence of the role played by the C-terminal domain of lamin A...

..The aim of this review is to attempt a genotype-phenotype correlation and speculate on common pathogenic mechanisms underlying this disease...

..We therefore sought to develop a method to quantify relative levels of sarcolemma-associated proteins using digitally captured images of immunolabelled sections of skeletal muscle...

..Linkage analysis to the three collagen VI genes was performed in all informative families (n = 7), whereas immunohistochemical analysis of collagen VI expression in muscle was performed in the remaining cases...

..In addition, we show that there is a tissue-specific difference in the developmental expression of the laminin alpha 2 protein...

..In contrast, immunohistochemical analysis of skin biopsies may not always reveal an underlying collagen VI defect...

..These results suggest the generation of a mouse model for FKRP related muscular dystrophy requires a knock-down rather than a knock-in strategy in order to give rise to a disease phenotype...

..We evaluated possible predictive factors for scoliosis development in a large DMD population...

..With the exception of one family in which two generations were affected, inheritance appeared autosomal-recessive or sporadic in all cases...

..Here we have investigated laminin alpha2 deficiency in skin biopsy specimens from two patients with congenital muscular dystrophy...

..Larger prospective randomised, double-blind, placebo-controlled trials with salbutamol will be needed to confirm these preliminary findings...

..Immaturity of fibres, however, needs to be taken into account, especially in neonates...

..These findings extend the phenotypes within the CMD classification...

..These results suggest that, by using appropriate sequences, mild white matter changes may be detectable on brain magnetic resonance imaging in the first days of life in infants with merosin-deficient congenital muscular dystrophy...

..Mutation analysis of the collagen 6 genes in cases with normal collagen VI expression is needed to resolve this issue...

..We suggest these abnormalities of alpha-dystroglycan are caused by its defective glycosylation and are integral to the pathology seen in MDC1C...

....

..These seven infants are affected by a myopathic condition clinically resembling SMARD1. However, its pathogenesis appears to be a myopathy affecting predominantly the diaphragm...

..This guides rational therapy and multidisciplinary management, which may be crucial for survival, particularly in pedigrees where previous deaths have occurred in infancy...

..Our report underlines the complexity of the pathogenic mechanism leading to X-linked dilated cardiomyopathy but suggests that differences in tissue-specific expression of dystrophin mutations may be a common feature in this condition...

..Molecular genetic studies in one family identified a V4849I homozygous missense mutation in the RYR1 gene. This report suggests a congenital myopathy associated with recessive RYR1 mutations...

..Genetic studies excluded involvement of the SMN gene, or of other genes located on chromosome 5q, confirming that this syndrome represents a different entity from typical proximal spinal muscular atrophy...

..Flow cytometry analysis provides an alternative method for screening for collagen VI deficiency at the protein level in a quantitative, time and cost-effective manner...

..The results are easy to interpret in families with total absence of the protein, while caution is required when dealing with families where partial expression occurs...

..We conclude that mutations in the potassium channel gene (KCNA1) can cause severe neuromyotonia resulting in marked skeletal deformities even if episodic ataxia is not prominent...

..It is also important to study the expression of laminin alpha 2 with more than one antibody...

..Systematic mutation analysis of these 6 glycosyltransferases in patients with a dystroglycan glycosylation disorder identifies mutations in approximately 65% suggesting that more genes have yet to be identified...

..The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of alpha-dystroglycan...

..We examined the prevalence, genotype-phenotype correlation, and natural history of lamin A/C gene (LMNA) mutations in subjects with dilated cardiomyopathy (DCM)...

..Understanding more about which muscles are affected in children with congenital myopathies may provide information on the underlying pathological process and help in the search for candidate proteins and genes...

..Several curative therapeutic strategies including cell and gene therapy are being pursued but are still at an experimental stage...

..The identical clinical and imaging features of the sporadic and familial cases suggest that these cases are likely to be affected by the same condition...

..Data have been validated independently in the different model systems used, and the studies describe a rational collaborative path for the preclinical selection of AOs for evaluation in future clinical trials...

..These findings suggest that factors other than mobility are likely to have an effect on SMA bone mineral density...

..This is the first description of mutations in the human LARGE gene and we propose to name this new disorder MDC1D...

..These data indicate that it is not always possible to correlate clinical course and alpha-dystroglycan labeling and suggest that there might be differences in alpha-dystroglycan processing in these disorders...

..Our findings suggest that complex rearrangements have to be considered in typically affected males with X-linked myotubular myopathy...

....

..This case emphasizes that investigation of the MTM1 gene and X-inactivation studies are indicated in isolated females with histopathological and clinical findings suggestive of myotubular myopathy...

..We hypothesise that the 5' region of the dystrophin intron 11, containing common target areas for the insertion of mobile elements, may have a role in the rearrangement of this novel Alu-like sequence...

..In this review we present the major molecular, clinical and diagnostic aspects of each group of congenital muscular dystrophy with an emphasis in the more recent developments...

..To assess the clinical course and genotype-phenotype correlations in patients with selenoprotein-related myopathy (SEPN1-RM) due to selenoprotein N1 gene (SEPN1) mutations for a retrospective cross-sectional study...

..In addition, it shows the diversity of pathological features that can occur in congenital myopathies due to mutations in the same gene...

..Mutations in these five glycosyltransferase genes were detected in 34% of patients indicating that, after the exclusion of FKRP, the majority of patients with a dystroglycanopathy harbour mutations in novel genes...

..These results show that glucocorticoids confer their benefit to dystrophic muscle in a complex fashion, culminating in a switch to a more normal muscle fiber type...

..This information will be of help for the development of therapeutic approaches aimed at restoring dystrophin levels sufficient to prevent the muscle pathology in DMD...

....

..This paper aims to highlight these conditions as the common differentials or more difficult to diagnoses to consider in patients presenting as CMD...

..Our data suggest the existence of a disease spectrum of CMD including brain and eye abnormalities resulting from POMT1 mutations...

....

..LARGE and/or LARGE-L up regulation could therefore represent a therapeutic option for patients affected by dystroglycanopathies, regardless of their primary defect...

..We provide insight into the natural history of scoliosis in DMD that should help families and clinicians with decision-making when surgery is considered...

..Linkage analysis excluded all the known loci for CMD. We propose that this may represent a novel variant of CMD...

..This review outlines the genetic basis of these "non-sarcolemmal" forms of dystrophy and discusses current ideas on their pathogenesis...

....

..Mutations in protein-O-mannose-beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) have been found in muscle-eye-brain disease, a congenital muscular dystrophy with structural eye and brain defects and severe mental retardation...

....

..These observations imply a specific role for FKRP during striated muscle, neuronal and glial development and suggest that protein mis-localisation is not a common mechanism of disease in FKRP-related dystrophies...

..This article provides an overview of the clinical, biochemical and genetic features of this group of disorders...

..The aim of this study was to determine the genetic defect in two white families with a dystroglycanopathy...

....

..Late-onset congenital myopathies may be under-recognised and diagnosis requires a high degree of clinical suspicion...

..Furthermore, the cultured cell system used can serve as a suitable model to study human alternative splicing...

..The infantile neuromuscular form of glycogen storage disease type IV is considered extremely rare, but our encountering two patients in close succession suggests that the disease may be underdiagnosed...

..The present study represents the first identification of a gene responsible for classical MmD, demonstrates its genetic heterogeneity, and reassesses the nosological boundaries between MmD and RSMD...

..Immunodetection of reduced laminin beta1 may be a useful secondary marker in adults with this disorder, as immunocytochemistry of lamins is not yet of diagnostic use...

..In addition, they may also be relevant to studies of fibre type plasticity and diversity in nemaline myopathy...

..Animal models are helping to elucidate the function of some of these proteins, to develop therapeutic strategies and to suggest candidate proteins for other neuromuscular disorders...

....

..These observations raise the possibility that mutations in the gene encoding for syncoilin may underlie some forms of muscle disease...

..This review reports on the use of muscle magnetic resonance imaging as a clinical and research tool in inherited neuromuscular disorders...

..MDC1C patients either carried 2 missense or 1 missense and 1 nonsense mutations. Patients with LGMD2I shared a common mutation (C826A,Leu276Ileu) and their phenotypic severity was correlated with the second allelic mutation...

....

..The striking response also suggests that there may be an optimal window for treatment of Duchenne dystrophy in the early stages of the disease...

....

..This study further highlights the central role that dystroglycan has in neuronal migration...