Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that patients with autosomal recessive merosin deficient congenital muscular dystrophy (CMD), as opposed to the merosin positive cases form a homogeneous subgroup of a clinically more severe form of CMD. We examined merosin expression in muscle biopsies from five children with the severe classical form of CMD. Merosin deficiency was found only in 1 patient, a 6-year-old female, with abnormal brain myelination. However, her initial biopsy did not reveal the classical picture of dystrophy. The four merosin positive cases exhibited severe muscle weakness but their brain imagings were normal. There were no familial cases, except for the mother of 1 patient who had a milder form of the disease, suggesting an autosomal dominant mode of inheritance. In contrast to previous reports, the merosin deficient CMD cases were rare in our group. Furthermore, merosin positive cases were also associated with severe phenotype suggesting that a severe phenotype is not exclusive to merosin deficient cases. Finally, the absence of merosin in a neonate with hypotonia and weakness can be helpful in making a definitive diagnosis of CMD, even though the dystrophic process may not be evident yet and histology may be non-specific.
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PMID:Severe classical congenital muscular dystrophy and merosin expression. 978 20

The congenital muscular dystrophies are a heterogeneous, recessively inherited group of disorders that have been subclassified on the basis of clinical central nervous system involvement. We report two children with "pure" congenital muscular dystrophy, one merosin negative and one merosin positive with extensive white matter and occipital cortical neuromigration abnormalities on magnetic resonance imaging (MRI). The first patient (merosin-negative congenital muscular dystrophy) presented with hypotonia and weakness in the neonatal period and subsequently was found to have a leukoencephalopathy and occipital cortical dysplasia on magnetic resonance imaging. The second patient presented with developmental delay without definite weakness. Initial investigations revealed a leukoencephalopathy and cortical dysplasia, but the patient subsequently was shown to have merosin-positive congenital muscular dystrophy. These patients illustrate that white-matter changes are not specific for merosin-negative congenital muscular dystrophy alone and that extensive cortical abnormality can be found in both groups of patients. In addition, our second patient illustrates a nonmuscular mode of congenital muscular dystrophy presentation that should be considered in patients with a "nonprogressive leukodystrophy."
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PMID:Congenital muscular dystrophy, white-matter abnormalities, and neuronal migration disorders: the expanding concept. 979 53

We report two siblings, an 11-year-old boy and his 7-year-old sister, referred to us with a diagnosis of muscular dystrophy. The boy presented at 22 months with delay in walking. A very high serum creatine kinase (CK) level and a dystrophic muscle biopsy lead to a diagnosis of Duchenne muscular dystrophy prior to the identification of the dystrophin gene. Two years later his sister presented with similar problems. A diagnosis of limb-girdle muscular dystrophy was made when they were shown to have inherited different X-chromosomes and normal expression of dystrophin and all sarcoglycans. Their conditions remained static. Recently a slowing of the peripheral motor nerve conduction velocities and T2-weighted brain magnetic resonance imaging showed increased signal of the white matter, both of which are features of merosin-deficient congenital muscular dystrophy. Immunolabelling using a C-terminal laminin alpha 2 chain antibody showed a reduction in expression, while labelling with another antibody that recognises a 300-kDa fragment showed a very significant reduction. Mutational analysis of the LAMA2 gene showed two mutations: one was a G-->C point mutation at position -1 of intron 28 acceptor splicing site. This mutation induced activation of a cryptic splice at nucleotide 4429 of exon 29 and partial skipping of this exon, with conservation of the open reading frame. The other was a nonsense mutation due to a C_T transition at position 5525 of the cDNA sequence (exon 37), resulting in a stop codon. These data confirm that mutations of the LAMA2 gene that do not completely disrupt the production of the protein can give rise to phenotypes considerably milder than classical merosin-deficient congenital muscular dystrophy. Partial laminin alpha 2 deficiency should be considered in the differential diagnosis of limb-girdle muscular dystrophy.
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PMID:Laminin alpha 2-chain gene mutations in two siblings presenting with limb-girdle muscular dystrophy. 982 80

We present the MRI findings in five patients with congenital muscular dystrophy (CMD) and merosin (laminin alpha2) deficiency, which was total in one and partial in four. In one patient with partial merosin deficiency, MRI was normal. The other four patients had supratentorial white matter abnormalities. In three, T2-weighted images revealed subcortical, deep lobar and periventricular high signal in white matter, while in the other there were only small peritrigonal areas of increased signal. On T1-weighted images, there was slightly low signal. Cortical abnormalities were absent. None of these changes were accompanied by symptoms or signs of central nervous system involvement. White matter abnormalities in a patient with CMD should prompt investigation of merosin.
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PMID:Congenital muscular dystrophy with merosin deficiency: MRI findings in five patients. 987 36

The dy/dy mouse is an animal model for human merosin-negative congenital muscular dystrophy (CMD), which has been reported to have reduced or no expression of the basement membrane protein laminin alpha2. We here investigate various myogenic and nonmyogenic tissues of mature dy/dy and control 129ReJ mice histologically and for laminin alpha2 expression. In addition, expression patterns of laminin alpha1, alpha2, alpha4, and alpha5 chains, the interstitial proteins fibronectin and tenascin-C, and the adhesion molecules VCAM-1, ICAM-1, and alpha4 integrin were characterized in skeletal muscle of 1- and 7-day and mature (>6 weeks old) dy/dy and control 129ReJ mice. The laminin alpha2 chain remained detectable in myogenic tissues of dy/dy mice by immunofluorescence using two different monoclonal antibodies and by Northern blot analysis. However, laminin alpha2 expression was significantly reduced or not detectable in nonmyogenic tissues of dy/dy mice, including skin, lung, kidney, brain, thymus, and eye. Focal lesions were observed in mature skeletal muscle only, characterized by necrotic tissue, isolated VCAM-1- and ICAM-1-positive cells indicative of inflammatory processes, and regenerating muscle fibers surrounded by intense tenascin-C and fibronectin expression. In contrast to studies on human CMD muscle, laminin alpha1 was not detectable in either dy/dy or control skeletal muscle using immunofluorescence or Northern blot analysis. Immunofluorescence localized laminin alpha4 to basement membranes of blood vessels, the endoneurium of the intramuscular nerves, and the neuromuscular junction in skeletal muscle of 1- and 7-day-old dy/dy and control mice. In mature muscle, laminin alpha4 expression shifted to the perineurium of intramuscular nerves in both dy/dy and control mice. Furthermore, strong upregulation of laminin alpha4 in the basement membranes of blood vessels, the perineurium of intramuscular nerves, and of isolated regenerating muscle fibers in the dy/dy mice was apparent. Investigation of 1-day-old animals revealed expression of laminin alpha5 in skeletal muscle fiber basement membranes of dy/dy but not control animals. This difference between dy/dy and control animals was no longer apparent at 7 days after birth, indicating a temporary shift in expression pattern of laminin alpha5 in dy/dy animals. Analysis of the extracellular matrix components of 1- and 7-day-old dy/dy and control skeletal muscle revealed an early onset of the dystrophy, even before histopathological features of the disease were evident. Our data confirm the absence of laminin alpha1 chain in myogenic tissues of both dy/dy and control mice and suggest compensation for reduced laminin alpha2 in dy/dy skeletal muscle by laminin alpha4 and, in early development, also laminin alpha5. These results have significant ramifications in the diagnosis of human merosin-negative CMD.
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PMID:Expression of laminin alpha1, alpha2, alpha4, and alpha5 chains, fibronectin, and tenascin-C in skeletal muscle of dystrophic 129ReJ dy/dy mice. 988 26

Children with merosin-deficient congenital muscular dystrophy (CMD) have striking white matter changes on T-2 weighted brain magnetic resonance imaging (MRI). There have been occasional cases with structural abnormalities, mainly involving the occipital cortex. We report our brain imaging findings in 14 children with merosin-deficient CMD. Ten cases had a severe reduction or absence of merosin on immunocytochemistry and four cases had partial reduction. All 14 cases had white matter changes, which appeared after the first 6 months of life and persisted with time. The changes were diffuse and the oldest child scanned (14 years) also showed involvement of the U fibres. Five children with total absence of merosin also had structural abnormalities. One child had moderate mental retardation and epilepsy, mainly characterised by complex partial seizures, with atypical absences, which had been difficult to treat. Brain MRI showed marked occipital agyria and pontocerebellar hypoplasia. The gyral pattern of the rest of the brain looked normal. The four other cases, all with normal intelligence, also had cerebellar hypoplasia with variable involvement of the pons. They did not, however, have neuronal migration defects. It is recognised that several forms of congenital muscular dystrophy, namely Fukuyama CMD, muscle-eye-brain disease and Walker-Warburg syndrome, have structural brain abnormalities and associated severe mental retardation. Our cases demonstrate that a range of structural malformations can also be found in a significant number of children with merosin-deficient CMD.
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PMID:Merosin-deficient congenital muscular dystrophy: the spectrum of brain involvement on magnetic resonance imaging. 1022 Aug 62

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.
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PMID:Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study. 1022 Aug 63

Large families with congenital muscular dystrophy are rare. We report a clinical, histopathological, immunocytochemical, electrophysiological, radiological and genetic study of 10 cases affected by "pure" CMD belonging to two generations of a large inbred Palestinian family. The disease showed autosomal recessive inheritance. All patients had generalised muscular weakness and hypotonia at birth without arthrogryposis. They had a relatively benign clinical course with stabilisation of the clinical picture at different ages and at variable degrees of severity. The pattern of muscle weakness and wasting was more marked in the proximal upper limb-girdle and trunk muscles. Lower limb muscles were more mildly involved. Serum CK was normal or moderately increased. All patients had normal intelligence, normal computed tomography (CT) scans of the brain and normal somatosensory evoked potentials (SEP). Electromyography (EMG) and muscle biopsy showed morphological changes compatible with muscular dystrophy. Immunocytochemistry for dystrophin, laminin alpha 2 of merosin, and for alpha, beta, gamma sarcoglycans was normal. Linkage analysis excluded all the known loci for CMD, including laminin alpha 2 on chromosome 6q2, the Fukuyama congenital muscular dystrophy locus on 9q3, the integrin alpha 7 locus on chromosome 12q13 and the recently identified locus on 1p35-36. The family we present is clinically and genetically distinct from the already mapped forms of congenital muscular dystrophy. Genetic studies are in progress to localise the gene responsible for this condition.
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PMID:Merosin-positive congenital muscular dystrophy: a large inbred family. 1022 57

A multiplex system of Western blotting is presented in which most of the current muscular dystrophy proteins can be analyzed simultaneously on one pair of blots. This represents a significant improvement in efficiency and cost for this type of analysis. The final diagnosis is more quickly achieved in patients where several possible diagnoses are indicated after clinical appraisal, and those with unusual presentations may be quickly resolved. The method uses a biphasic polyacrylamide gel system, which enables the corresponding blot to be probed simultaneously with a cocktail of monoclonal antibodies. The gel is optimized so that large proteins of more than 200 kd (eg, dystrophin, dysferlin, and myosin heavy chain) can be analyzed in the top part, while smaller proteins under 150 kd (eg, calpain 3, the 80-kd fragment of laminin alpha2 chain, all of the sarcoglycans, and caveolin 3) are separated in the lower phase. This basic system could be used for different combinations of antibodies as new muscular dystrophy proteins are identified and require examination. In addition, analysis of the laminin alpha2 chain of merosin showed that this protein was expressed as a doublet or triplet set of bands in many patients with active muscle pathology. This may indicate the existence of an embryonic isoform, which is re-expressed in regenerating fibers.
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PMID:Multiplex Western blotting system for the analysis of muscular dystrophy proteins. 1023 40

Feeding difficulties were assessed in 14 children (age range 2-14 years) with merosin deficient congenital muscular dystrophy, a disease characterised by severe muscle weakness and inability to achieve independent ambulation. Twelve of the 14 children were below the 3rd centile for weight. On questioning, all parents thought their child had difficulty chewing, 12 families modified the diet, and 13 children took at least 30 minutes to complete a meal. On examination the mouth architecture was abnormal in 13 children. On videofluoroscopy only the youngest child (2 years old), had a normal study. The others all had an abnormal oral phase (breakdown and manipulation of food and transfer to oropharynx). Nine had an abnormal pharyngeal phase, with a delayed swallow reflex. Three of these also showed pooling of food in the larynx and three showed frank aspiration. These six cases all had a history of recurrent chest infections. Six of eight children who had pH monitoring also had gastro-oesophageal reflux. As a result of the study five children had a gastrostomy, which stopped the chest infections and improved weight gain. This study shows that children with merosin deficient congenital muscular dystrophy have difficulties at all stages of feeding that progress with age. Appropriate intervention can improve weight gain and reduce chest infections. The severity of the problem has not been previously appreciated in this disease, and the study shows the importance of considering the nutritional status in any child with a primary muscle disorder.
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PMID:Feeding problems in merosin deficient congenital muscular dystrophy. 1033 4


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