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Query: UMLS:C0026850 (muscular dystrophy)
 5,870 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

About half of the children with classical congenital muscular dystrophy (CMD) show an absence in their skeletal muscle of laminin alpha2 chain, one of the components of the extracellular matrix protein, merosin. Linkage analysis implicated the laminin alpha2 chain gene (LAMA2) on chromosome 6q2, now confirmed by the discovery of mutations in the laminin alpha2 chain gene. We have further investigated the location of the LAMA2 locus on chromosome 6q2, using both linkage analysis in nine informative families and homozygosity mapping in 13 consanguineous families. Four of these families only had mild or moderate down regulation of laminin alpha2 chain expression and a milder phenotype; the rest had no protein or only a trace. Haplotype analysis in all the informative families, including those with partial laminin alpha2 expression, was compatible with linkage to chromosome 6q2. This observation expands the spectrum of the phenotype secondary to laminin alpha2 chain deficiency. Our results suggest that the LAMA2 locus is more centromeric than previously proposed. Recombinant events place the locus between markers D6S470 and D6S1620 in an interval of less than 3 cM.
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PMID:Refinement of the laminin alpha2 chain locus to human chromosome 6q2 in severe and mild merosin deficient congenital muscular dystrophy. 903 83

We report the clinical features and the muscle pathology in 2 patients with congenital muscular dystrophy (CMD) secondary to merosin deficiency and in 2 patients with sarcoglycan (adhalin) deficiency. Electron microscopic examination revealed sarcolemmal defects in non-necrotic muscle fibers in all cases. These pathological findings are indistinguishable from those of Duchenne/Becker muscular dystrophy. We suggest that the similarities in histological findings reflect a common pathogenetic mechanism, i.e., a structural weakening of the sarcolemma with an increased susceptibility to rupture under mechanical stress. We propose the term sarcolemmopathy as an all-encompassing rubric for these disorders.
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PMID:Muscle pathology and clinical features of the sarcolemmopathies. 904 10

We report on two sisters of first degree cousin parents who were born with severe hypotonia, arthrogryposis multiplex congenita (AMC) and dysmorphic features consistent with the fetal akinesia/hypokinesia sequence. They needed assisted ventilation and each died at the age of 5 months. Both had type II lissencephaly (cobblestone lissencephaly) which was visualized by magnetic resonance imaging (MRI) in the proband. Ophthalmic evaluation revealed no ocular malformations in either of them. Brain auditory evoked potentials (BAEP) revealed bilateral severe sensorineural hearing loss in the proband, whereas an MRI-guided open muscle biopsy of the sartorius muscle (the only remaining thigh muscle) showed features of muscular dystrophy. Immunohistochemistry revealed normal dystrophin, dystrophin-associated glycoproteins (DAG) and merosin. Certain clinical and pathological features distinguish the disease seen in these sisters from reported isolated cases where lethal AMC was associated with brain dysplasia and from the main syndromes of congenital muscular dystrophy/cobblestone lissencephaly. Differences from the Walker-Warburg syndrome, which simulates it in severity, included the absence of severe hydrocephalus, normal creatine kinase (for age) and minimal (mainly periventricular) white matter abnormalities. The findings suggest either an independent entity, in the studied family, or an allelic variation of the cobblestone lissencephaly (type II lissencephaly) syndrome.
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PMID:Lethal congenital muscular dystrophy in two sibs with arthrogryposis multiplex: new entity or variant of cobblestone lissencephaly syndrome? 905 48

Two siblings with a congenital muscular dystrophy and severe mental retardation which was not due to dystrophin, merosin, or adhalin deficiency are described. These cases overlap with congenital muscular dystrophy of the Fukuyama-type but are less severe. Atypical features include limited facial involvement, retained ambulation, and severe retrocollis.
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PMID:Congenital muscular dystrophy with severe retrocollis and mental retardation: a report of two siblings. 906 86

Complete or partial deficiency of the laminin alpha2 chain of merosin has been demonstrated in a proportion of children with classical congenital muscular dystrophy and linkage to the laminin alpha2 chain gene (LAMA2) on chromosome 6q2 has been established. As the laminin alpha2 chain is also expressed in the trophoblast, its detection and linkage analysis are useful tools for prenatal diagnosis. We report our experience of seven prenatal diagnoses in families with partial deficiency or total absence of the laminin alpha2 chain in the muscle of the propositi. In five instances, expression of the laminin alpha2 chain in the trophoblast was normal and linkage data suggested that the fetuses were unaffected. In one family, the immunocytochemical studies of the trophoblast showed the absence of laminin alpha2, suggesting that the fetus was affected. Linkage analysis confirmed that the fetus had inherited the two at-risk haplotypes. In one family with partial laminin alpha2 chain deficiency, the haplotype analysis was hampered by maternal DNA contamination. Immunocytochemical analysis of chorionic villus sampling showed a reduction in laminin alpha2 expression. The pregnancy was presumed to be at high-risk and terminated. However, subsequent analysis of fetal DNA indicated that the fetus was probably heterozygous. Our data suggest that immunocytochemical analysis of the trophoblast can detect abnormalities in affected fetuses and gives normal results in unaffected and carrier fetuses. Nevertheless, we recommend that linkage analysis to the LAMA2 locus is also studied in all cases.
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PMID:The role of immunocytochemistry and linkage analysis in the prenatal diagnosis of merosin-deficient congenital muscular dystrophy. 909 47

Merosin-deficient congenital muscular dystrophy (CMD) is an autosomal recessive condition usually with onset at birth or within the first months of life. Affected children are severely disabled and usually do not achieve the ability to walk without support. They invariably have white matter abnormalities on brain magnetic resonance imaging (MRI). We report a 29-year-old man with a late childhood onset limb-girdle type muscular dystrophy and cerebral white matter changes on MRI. Immunocyto-chemical studies of the patient's muscle biopsy showed a reduction in expression of the laminin alpha 2 chain of merosin. The patient had three affected siblings, and microsatellite genotyping confirmed linkage to the laminin alpha 2 locus (LAMA2) on chromosome 6q2 in this family. This case probably represents a milder allelic variant of classical merosin-deficient CMD. Merosin status should be assessed in patients with late-onset limb girdle muscular dystrophy.
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PMID:Late onset muscular dystrophy with cerebral white matter changes due to partial merosin deficiency. 913 48

The aim of this study is to localize the alpha 2 laminin chain in normal human skin. The methods used were immuno-gold cytochemistry on cryo-ultramicrotomy sections and thin-section-fracture-label, together with electron microscopy observation. Results were compared with light microscopy peroxidase immuno-staining. Both normal skin samples and skin biopsies from laminin alpha 2 chain deficient congenital muscular dystrophy affected patients were studied. The results show that, in normal skin, the laminin alpha 2 chain is spread throughout the cytoplasm of basal keratinocytes, while it appears associated with desmosomal tonofilaments in the spinous and granular epidermal layers; in skin samples from dystrophic patients the laminin alpha 2 chain was not detectable. These data suggest that the function of the laminin alpha 2 chain is different in the epidermis as compared to that in muscle and peripheral nerve, where it is localized in the basement membrane.
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PMID:Intracellular detection of laminin alpha 2 chain in skin by electron microscopy immunocytochemistry: comparison between normal and laminin alpha 2 chain deficient subjects. 913 49

Merosin, also called laminin-2, is an isoform of laminin comprised of the alpha 2, beta 1 and gamma 1 chains. Deficiency of merosin alpha 2 chain was recently identified as the primary cause of the classical form of congenital muscular dystrophy (CMD), an autosomal recessive neuromuscular disorder characterised by muscular dystrophy and brain white matter abnormalities. Interestingly, merosin-deficient CMD and its animal model dy mouse are also accompanied by dysmyelination of peripheral motor nerves. In peripheral nerve, merosin is expressed in the endoneurium surrounding the Schwann cell/myelin sheath, while the putative merosin receptors dystroglycan and alpha 6 beta 4 integrin are expressed in the outer membrane of Schwann cell/myelin sheath. Together with the well known fact that the deposition of laminin in the basement membrane is essential for Schwann cell myelination, these findings indicate that the interaction of merosin with dystroglycan and/or alpha 6 beta 4 integrin plays an important role in peripheral myelinogenesis and that the disturbance of this interaction leads to peripheral dysmyelination in merosin deficiency. The clinical significance of peripheral dysmyelination in merosin deficiency is also discussed.
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PMID:Peripheral nerve involvement in merosin-deficient congenital muscular dystrophy and dy mouse. 913 44

Approximately half the cases of classical congenital muscular dystrophy (CMD) have a pronounced deficiency or absence of the laminin alpha 2 chain of laminin-2 (merosin). This is caused by mutations in the LAMA2 gene that codes for laminin alpha 2, and all informative cases so far studied show linkage to the appropriate region on chromosome 6q. Most CMD patients with a deficiency of laminin alpha 2 have a severe phenotype that involves skeletal muscle, and the central and peripheral nervous system. We have identified four cases that have minimal reduction of laminin alpha 2 using a commercial antibody that only recognises a C-terminal 80 kDa fragment, but show a pronounced reduction using an antibody to the 300 kDa fragment. Haplotype analysis is compatible with linkage to the LAMA2 locus in three informative families, whilst the fourth family was not informative. Two of the affected children are ambulant and have a mild phenotype. The third case is unusual in having severe muscle weakness but does not show the white matter changes on magnetic resonance imaging of the brain that is usually seen in merosin-deficient cases of CMD; the fourth case has a severe phenotype, typical of merosin-deficient patients but shows good immunolabelling of the 80 kDa fragment of laminin alpha 2, corresponding to the C-terminal region. Our data show that there is a broad spectrum of phenotype and protein expression associated with a primary deficiency in laminin alpha 2, and that a wider range of clinical cases need to be screened for a deficiency of merosin. It is also important to study the expression of laminin alpha 2 with more than one antibody.
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PMID:Variable clinical phenotype in merosin-deficient congenital muscular dystrophy associated with differential immunolabelling of two fragments of the laminin alpha 2 chain. 918 80

Prenatal diagnosis was carried out in five merosin-deficient congenital muscular dystrophy (CMD) families. We studied both laminin-alpha 2 chain expression in trophoblast using immunocytochemistry and linkage analysis to the LAMA2 locus. In four families there was good agreement between the immunocytochemistry and linkage analysis results: in one case the trophoblast was negative for LAMA2 expression and haplotype analysis suggested the foetus was affected; in the other three cases the laminin-alpha 2 chain expression was normal and foetuses were found to be carriers. In the remaining family, a case of partial laminin-alpha 2 chain expression, the immunostaining of the trophoblast was weaker compared to the control. Linkage analysis, however, could not be performed because of maternal DNA contamination. After termination of pregnancy, the foetal muscle was studied and suggested weak laminin-alpha 2 chain expression. The haplotype analysis however showed that the foetus was probably a carrier, unless a double recombinant event had occurred. We conclude that a combination of immunocytochemistry and linkage analysis can be used for the prenatal diagnosis of merosin deficient CMD. 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.
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PMID:Prenatal diagnosis in merosin-deficient congenital muscular dystrophy. 918 81


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