1/63. 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 = 1keywords = lamina, membrane (Clic here for more details about this article) |
2/63. 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 = 0.8264345346172keywords = lamina (Clic here for more details about this article) |
3/63. Decreased expression of laminin beta 1 in chromosome 21-linked Bethlem myopathy.Muscle biopsies of four patients affected by chromosome 21-linked Bethlem myopathy were investigated by means of immunohistochemistry, with monoclonal antibodies for laminin chains, dystrophin and dystrophin associated glycoproteins. The objective of this study was to determine whether an altered molecular structure of collagen type vi, characteristic of Bethlem myopathy, could influence the expression of the protein complex linking the extracellular matrix with the subsarcolemmal cytoskeleton. Normal expression of all proteins was found except for laminin beta 1, along with an age related progressive deficiency of this protein in the muscle fibre basal lamina. This study shows that Bethlem myopathy linked to chromosome 21 is associated with a secondary decrease in laminin beta 1 expression.- - - - - - - - - - ranking = 0.8264345346172keywords = lamina (Clic here for more details about this article) |
4/63. calcium homeostasis and ultrastructural studies in a patient with limb girdle muscular dystrophy type 2C.There is increasing evidence that gamma-sarcoglycan is absent and other sarcoglycans are reduced in patients with the limb-girdle muscular dystrophy type 2C (LGMD2C) form of severe childhood autosomal recessive muscular dystrophy. In the present investigation, we combined microspectrofluorimetry and electron microscopy techniques to investigate the physiological function and the ultrastructure of control and LGMD2C myotubes. Results obtained from Ca2 measurements showed that the resting level of the cytosolic free calcium ([Ca2 ]i ) in control myotubes was 73 /-3.4 nmol/l (mean /-se, n=35) and in LGMD2C myotubes was 69 /-4 nmol/l (n=44). carbachol (CCh, 10 micromol/l ) induced a 335 /-10 nmol/l (n=8) rise in [Ca2 ]i in control myotubes and 531.9 /-32 nmol/l (n=23) in LGMD2C myotubes. Similarly, elevations of [Ca2 ]i by 35 mmol/l K were 324 /-32 nmol/l (n=8) in control myotubes and 442.8 /-24 nmol/l (n=22) in LGMD2C myotubes. caffeine (10 mmol/l) activated similar [Ca2 ]i peaks in control and LGMD2C myotubes but induced a biphasic response in LGMD2C in four out of 12 myotubes and only a monophasic response in control myotubes. The ultrastructural results showed that the plasma membrane was abnormally indented and convoluted in both the LGMD2C biopsy and the LGMD2C cultured myotubes. It is suggested that the reduction in components of the dystrophin-glycoprotein complex results in the instability and an increase in the surface area of the plasma membrane, which may result in a higher population of Ca2 channels in the LGMD2C myotubes.- - - - - - - - - - ranking = 0.34713093076559keywords = membrane (Clic here for more details about this article) |
5/63. Multiple episodes of thrombosis in a patient with Becker muscular dystrophy with marked expression of utrophin on the muscle cell membrane.We previously reported a patient with Becker muscular dystrophy (BMD) who exhibited a benign clinical phenotype and marked expression of utrophin on the muscle cell membrane. The patient developed multiple episodes of thrombosis (middle cerebral and femoral arteries) in the course of the disease. We re-examined the biopsy muscle specimen from the patient immunohistochemically as to the expression of procoagulant or anticoagulant factors. We found a lower expression of thrombomodulin on the muscle cell membrane in the BMD patient compared with other BMD or Duchenne muscular dystrophy (DMD) patients. Although utrophin up-regulation in muscle is thought to prevent the muscle wasting in dystrophin-deficient DMD or BMD, the data obtained in the present study indicate that up-regulated utrophin may have an unexpected influence on the function of the vascular or coagulation system.- - - - - - - - - - ranking = 1.0413927922968keywords = membrane (Clic here for more details about this article) |
6/63. Basal lamina abnormality in the skeletal muscle of walker-warburg syndrome.The basal lamina of skeletal muscle fibers has been reported to be thinned and disrupted in patients with Fukuyama and laminin-alpha-2-deficient congenital muscular dystrophies. The basal lamina is normal in other, later-onset, muscular dystrophies, but the plasma membrane is disrupted. It is unknown whether the dystrophic process in walker-warburg syndrome (WWS) is characterized by a basal laminal abnormality, a sarcolemmal abnormality, or both. The present study examined the skeletal muscle of a 3-month-old patient with WWS by immunohistochemistry and electron microscopy and compared the findings with control muscle samples. In control samples the basal lamina of skeletal muscle fibers was a continuous, uniformly dense structure associated with sarcolemma. In WWS the basal lamina appeared deranged, with disruptions in nonnecrotic muscle fibers. Furthermore, in some fibers the basal lamina was thinner, and in others, it was duplicated. dystrophin, laminin-alpha-2, and adhalin stains revealed normal immunoreactivity. The disruptions in the basal lamina may play a primary role in the degeneration of muscle fibers in WWS. When compared with the dystrophies with a primary sarcolemmal defect, it appears that those with primary basal lamina abnormalities (WWS, laminin-alpha-2-deficient, and Fukuyama congenital muscular dystrophies) present early in life, and the phenotype is more severe.- - - - - - - - - - ranking = 10.090779880789keywords = lamina, membrane (Clic here for more details about this article) |
7/63. Partial alpha-sarcoglycan deficiency with retention of the dystrophin-glycoprotein complex in a LGMD2D family.In patients with sarcoglycan (SG) deficiency, a primary defect in any one of the four SG proteins usually leads to reduced expression of the whole SG complex. We report a limb-girdle muscular dystrophy type 2D family (LGMD2D), with variable phenotype, where a mutation in the alpha-SG gene resulted in the partial deficiency of alpha-SG alone. The normal expression of the other three SG proteins suggests that mutations close to the alpha-SG transmembrane domain might be less critical for complex integrity, and that weakness may occur despite its retention.- - - - - - - - - - ranking = 0.1735654653828keywords = membrane (Clic here for more details about this article) |
8/63. Unusual laminin alpha2 processing in myoblasts from a patient with a novel variant of congenital muscular dystrophy.We recently described a novel congenital muscular dystrophy (CMD) syndrome characterized by mental retardation, microcephaly, and partial merosin deficiency on muscle biopsy. Linkage analysis excluded involvement of the known CMD loci. We now report on a study performed on the differentiation of cultured myoblasts from one patient affected by this condition to evaluate the potential to form myotubes and merosin processing in these cells. The differentiation rate was comparable to controls and myotubes were stable in culture. Biochemical analysis showed the expected 80-kDa merosin subunit in myoblasts. However, a shifted 60-kDa protein was detected in myotubes. Matrix-metalloproteinases (MMPs) zymography showed increased gelatinolytic activity, and immunoblotting identified an increased amount of membrane-type 1 matrix-metalloproteinase in pathological myotube preparations. Our results show that these CMD-derived myotubes contain a low molecular weight merosin. They further suggest that an altered regulation of MMPs can be involved in basal lamina damage.- - - - - - - - - - ranking = 1keywords = lamina, membrane (Clic here for more details about this article) |
9/63. Congenital muscular dystrophy with adducted thumbs, ptosis, external ophthalmoplegia, mental retardation and cerebellar hypoplasia: a novel form of CMD.At least six different forms of congenital muscular dystrophy are associated with structural changes of the central nervous system, and three of these have been mapped: merosin-deficient congenital muscular dystrophy on chromosome 6q2, Fukuyama congenital muscular dystrophy on chromosome 9q31, and muscle eye brain disease on chromosome 1p32. walker-warburg syndrome, congenital muscular dystrophy with calf hypertrophy, pontocerebellar hypoplasia, and normal eyes, and congenital muscular dystrophy with severe mental retardation and cerebellar cysts are nosologically distinct and have been excluded from the known congenital muscular dystrophy loci with structural changes of the central nervous system. Here, we describe a novel congenital muscular dystrophy syndrome which is phenotypically distinct from the recognized forms of congenital muscular dystrophy with brain involvement. Two siblings, a boy and a girl, were born to consanguineous parents from sicily. Both children were born with adducted thumbs and toe contractures. They were floppy from birth, walked late, showed profound generalized muscle weakness including facial muscles, elevated creatine kinase levels of 200-700U/l, and histological changes compatible with muscular dystrophy. In addition, both showed ptosis, external ophthalmoplegia, mild mental retardation, and mild cerebellar hypoplasia on MRI. Immunocytochemistry showed normal expression of muscle membrane proteins including laminin alpha 2, laminin beta 2, and alpha-dystroglycan. Linkage analysis excluded the candidate loci on chromosomes 6q2, 9q31, and 1q32. The gene locus for congenital muscular dystrophy 1B, MDC 1B, on chromosome 1q42 was also excluded. Adducted thumbs are a distinct clinical sign that has not been reported in congenital muscular dystrophy before and should facilitate recognition of further patients with this disorder.- - - - - - - - - - ranking = 0.1735654653828keywords = membrane (Clic here for more details about this article) |
10/63. Ullrich disease: collagen VI deficiency: EM suggests a new basis for muscular weakness.Ullrich disease is a form of congenital muscular dystrophy characterized clinically by generalized muscle weakness, contractures of the proximal joints, and hyperflexibility of the distal joints from birth or early infancy. Recently, mutations of the collagen VI gene have been associated with Ullrich disease. The authors report on a boy with Ullrich disease who has complete deficiency of collagen VI and harbors compound heterozygous mutations in the collagen VI alpha 2 gene. Absence of microfibrils on EM, together with normal collagen fibrils and basal lamina, suggests that loss of a link between interstitium and basal lamina may be a new molecular pathomechanism of muscular dystrophy.- - - - - - - - - - ranking = 1.6528690692344keywords = lamina (Clic here for more details about this article) |
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