1/579. A novel form of familial congenital muscular dystrophy in two adolescents.We report on two brothers (the product of first-degree consanguineous marriage; aged 15 and 12 years) who presented with severe hypotonia at birth, proximal muscle weakness associated with delayed motor milestones but normal cognitive function. Investigations (at 4 years of age) revealed mildly elevated serum creatine kinase (CK) levels (300 and 824 IU/l; N < or = 210). Muscle biopsies showed minimal change myopathy, no neurogenic atrophy but remarkable type-1 fibre predominance (up to 85.5%) without fibre-type disproportion. Clinical examination at 12 and 9 years, respectively, showed mild facial weakness and high-arched palate in both patients. The younger sibling also had ptosis but otherwise normal external ocular muscles. They showed symmetric proximal muscle weakness and wasting associated with calf-muscle hypertrophy. They could walk independently. A repeat muscle biopsy showed advanced dystrophic changes in the younger patient at the age of 10 years. Virtually all the remaining fibres were type 1. immunohistochemistry revealed normal expression of the dystrophin-glycoprotein complex (DGC), including dystrophin, beta-dystroglycan, alpha-(adhalin), beta-, gamma-, and delta-sarcoglycan, laminin-alpha2 chain (merosin) and syntrophin. Mild dystrophic features and type-1 fibre predominance (92.5%) were seen in the biopsy of the older patient, whereas immunohistochemistry showed normal expression of the DGC. Both cases also showed clear expression of integrin alpha7 at the muscle fibre surface and in the blood vessels. Three years later, they could still walk, but with difficulty, and the older brother showed enlargement of the tongue and echocardiographic features of left ventricular dilated cardiomyopathy.- - - - - - - - - - ranking = 1keywords = muscle, atrophy (Clic here for more details about this article) |
2/579. An unusual family of benign "X" linked muscular dystrophy with cardiac involvement.A family of benign X-linked muscular dystrophy is described. Two of the 3 affected members appear quite representative of Becker's dystrophy. A third shows no pseudohypertrophy, only gross atrophy, affecting proximal and distal muscles and also shows early onset contractures and electrocardiographic abnormalities and is in these ways much more representative of the variety described by Emery and Dreifuss (1966). Two of the cases have distinctly abnormal electrocardiograms with extensive and deep Q waves and abnormal R/S ratios and VI. Both these have shown progression of electrocardiographic abnormalities during a 2-year follow-up. The family is reported to document this very unusual occurrence.- - - - - - - - - - ranking = 0.22954537173586keywords = muscle, atrophy (Clic here for more details about this article) |
3/579. Muscle pain as a prominent feature of facioscapulohumeral muscular dystrophy (FSHD): four illustrative case reports.Clinical studies of facioscapulohumeral muscular dystrophy (FSHD) rarely report muscle pain as a significant feature of the condition. We report four adult patients with FSHD in whom muscle pain was a presenting complaint and remains their most disabling symptom. These four patients were investigated using a pain questionnaire and diary. Inflammatory and metabolic causes of muscle pain were sought by muscle biopsy and a range of biochemical investigations. All patients reported between three and seven different pains of varying site and nature. None of the group had more than one painfree day per month and all complained of disturbed sleep. While some pains could potentially be attributed to postural problems, others were clearly myalgic in nature, though most often not specifically exercise-related. These myalgic pains could be particularly difficult to control. Results of metabolic investigations and muscle biopsy revealed no clue to the pathogenesis of these pains and there was no evidence for any exceptional inflammatory response. We believe that pain in FSHD is an under-reported but significant symptom and that further work is necessary to determine its prevalence, understand its cause and provide effective treatment.- - - - - - - - - - ranking = 0.77045462826414keywords = muscle (Clic here for more details about this article) |
4/579. Cardiac transplantation in a Duchenne muscular dystrophy carrier.We report here for the first time the case of a symptomatic DMD carrier, who had a heart transplant for a severe dilated cardiomyopathy. dystrophin immunohistochemistry, western blot and analysis of X-chromosome inactivation on leucocytes, and skeletal and cardiac muscle biopsies on the explanted heart were performed. The patient was a heterozygote for exons 50-52 deletion in the dystrophin gene. The number of dystrophin-deficient fibres in the heart was much higher than in skeletal muscle. On the other hand, the explanted heart showed a non-skewed pattern of X-chromosome inactivation, as in leukocytes and skeletal muscle. The adverse cardiac course may be explained by the absence of regeneration among cardiomyocytes.- - - - - - - - - - ranking = 0.46227277695848keywords = muscle (Clic here for more details about this article) |
5/579. Newly recognized exons induced by a splicing abnormality from an intronic mutation of the dystrophin gene resulting in Duchenne muscular dystrophy. Mutations in brief no. 213. Online.A boy with the clinical phenotype of Duchenne muscular dystrophy had no detectable deletion or duplication in the dystrophin gene by the routine multiplex PCR method. In mRNA extracted from his muscle biopsy, newly recognized extra-exons of 172 bp and 202 bp were present between exon 25 and 26 suggesting a splicing abnormality. Genomic dna of the intron 25 including the above insertions were amplified and sequenced. There was one nucleotide substitution of A-to-G at 2 Kb downstream from the 5' end of intron 25 which formed consensus dinucleotide 'GT' motif for 5' splice site resulting in aberrant splicing. This is the first patient who had a mutation at the central part of an intron of the dystrophin gene instead of at the exon-intron border.- - - - - - - - - - ranking = 0.15409092565283keywords = muscle (Clic here for more details about this article) |
6/579. calpain III mutation analysis of a heterogeneous limb-girdle muscular dystrophy population.OBJECTIVE: To determine the frequency of calpain III mutations in a heterogeneous limb-girdle muscular dystrophy (LGMD) population. BACKGROUND: Mutations of the calpain III gene have been shown to cause a subset of autosomal recessive LGMDs. Patient populations studied to date have been primarily of French and Spanish origin, in which calpain III may cause 30% of autosomal recessive MDs. The incidence of calpain III mutations in non-French/Spanish MD patients has not been studied thoroughly. No sensitive and specific biopsy screening methods for detecting patients with abnormal calpain III protein are available. Thus, detection of patients relies on direct detection of gene mutations. methods: The authors studied the calpain III gene in 107 MD patient muscle biopsies exhibiting normal dystrophin. Muscle biopsy rna was produced for each patient, and the entire calpain III complementary dna was screened for mutations by reverse-transcriptase PCR/single-strand conformation polymorphism using three different conditions. RESULTS: The authors identified nine patients (eight unrelated) with causative mutations. Six of the seven distinct mutations identified are novel mutations and have not been described previously. CONCLUSION: The results suggest that approximately 9.2% of patients in the heterogeneous population with an LGMD diagnosis will show mutations of the calpain III gene. Interestingly, two patients were heterozygous for a single mutation at the dna level, whereas only the mutant allele was observed at the rna level. This suggests that there are undetectable, nondeletion mutations that ablate expression of the calpain III gene.- - - - - - - - - - ranking = 0.15409092565283keywords = muscle (Clic here for more details about this article) |
7/579. Pharyngeal dysphagia caused by isolated myogen dystrophy of musculus cricopharyngeus.Five patients suffering from idiopathic cricopharyngeal dysfunction (without Zenker's diverticulum) were treated surgically. Together with cricopharyngeomyotomy biopsies were taken at the level of the cricopharyngeus. Histological, enzyme hystochemical and electronmicroscopic examinations were performed on all patients. In two cases the histology revealed myogen dystrophy (presence of necrosis, myophagocytosis, abnormal fiber structure, basophilic fibers, fibrosis, mild cellular reaction and predominancy of fiber type I). Since the complete patient evaluation (clinical features, electromyography, serum creatinin phosphokinase level, etc.) could rule out any general, muscle disorders, the cause of the idiopathic pharyngeal dysfunction must have been in these two cases an isolated myogen dystrophy of the cricopharyngeus.- - - - - - - - - - ranking = 0.15409092565283keywords = muscle (Clic here for more details about this article) |
8/579. Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study.We report clinical, biopsy and autopsy findings in a merosin-deficient congenital muscular dystrophy (CMD) infant with abnormal cortical gyration. brain showed polymicrogyria and occipital agyria with marginal neuroglial heterotopia and inferior vermis hypoplasia. There was a normal pattern of myelination consistent with early age. laminin alpha 2 chain was also absent in myocardium, brain pial-glial membrane, brain and skin blood vessels as well as intramuscular and skin nerves. Occasional basal lamina gaps were found in muscle fibres but not in brain-blood vessels. This is the first autopsy study in a merosin-deficient CMD case with abnormal cortical gyration.- - - - - - - - - - ranking = 0.15409092565283keywords = muscle (Clic here for more details about this article) |
9/579. Merosin-positive congenital muscular dystrophy with transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.The congenital muscular dystrophies (CMDs) are a heterogeneous group of disorders. Among these, the laminin alpha 2 chain 'merosin' deficient CMD is caused by mutations of the LAMA2 gene on chr 6q2 and Fukuyama CMD is linked to chr 9q31. We report a 7-year-old boy who was born to consanguineous healthy parents. His motor and mental development were slow. creatine kinase (CK) was elevated (2.100 U/l), and the muscle biopsy was dystrophic. He sat unsupported at 12 months and took his first steps at 3 years of age. At 6 years of age he could walk up to 500 m. He was mentally retarded and spoke single words only. At 1 year, MR imaging of the brain showed abnormal increased periventricular T2-signal, consistent with dysmyelination as well as pontocerebellar hypoplasia and several cerebellar cysts. The pattern of gyration was normal. Follow-up at 4 years showed normalization of the previously abnormal periventricular T2-signal. Immunohistochemical analysis of the skeletal muscle showed normal expression of laminin alpha 2 for a C-terminal antibody and antibodies to the 300 and 150 kDa fragments, as well as of laminins alpha 5, beta 1, beta 2 and gamma 1. The boy has two healthy younger brothers. Linkage analysis excluded the candidate loci on chromosomes 6q2 and 9q31. As such, the patient's data are suggestive of a new form of laminin alpha 2 positive CMD characterized by transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.- - - - - - - - - - ranking = 0.30818185130566keywords = muscle (Clic here for more details about this article) |
10/579. Changes at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery-Dreifuss muscular dystrophy.Emery-Dreifuss muscular dystrophy (EDMD) is an X-linked recessive muscular dystrophy characterized by early contractures of the elbows, Achilles tendons and spine, slowly progressive muscle wasting and weakness, and cardiomyopathy associated with cardiac conduction defects. The emerin gene has been mapped to Xq28 and encodes a 34-kDa serine-rich protein, emerin, which has been localized to the nuclear envelope in a wide variety of tissues, including skeletal and cardiac muscle. Mutations spanning the emerin gene have been identified in patients with EDMD. We present here the effect, on emerin protein expression, of two missense mutations identified in unrelated EDMD patients. These alterations predict the replacement of a proline residue at position 183 with either a histidine or a threonine. Biochemical analysis has demonstrated that the mobility and expression levels of the mutant forms of emerin are indistinguishable from that of wild-type emerin, but that they have weakened interactions with nuclear lamina components. In comparison with the usual EDMD phenotype, patients with P183 missense mutations have a later age at onset of first symptoms, elbow contractures, ankle contractures, upper limb weakness and lower limb weakness, but there is no difference for the age at onset of cardiac involvement. This is the first report of protein studies on patients with missense mutations resulting in the clinical features of EDMD. These studies demonstrate the importance of proline 183 for the proper structure/function of emerin.- - - - - - - - - - ranking = 0.30818185130566keywords = muscle (Clic here for more details about this article) |
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