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)

A selective deficiency of a specific laminin isovariant, merosin made of M, B1 and B2 chains, was found in a series of 17 patients affected with congenital muscular dystrophy (CMD). The merosin deficiency was complete in 15 cases, and almost complete in two cases. An overexpression of the laminin A chain was seen in these biopsies, while B1 and B2 chains were normally expressed. Comparison of the clinical data with a series of 18 "merosin-non deficient" cases showed that the "merosin-deficient" cases were forming a more homogenous group than the "non-deficient" one. Hypotonia, contractures, motor development delay were generally more severe in the "merosin-deficient" series of cases. Moreover, white matter alterations were seen in most cases explored by MRI or scan imaging. A genetic linkage with a 6q2 locus, corresponding to the M chain gene localization, was found in a panel of informative families from French and Turkish origin with "merosin deficient" CMD. "Merosin non-deficient" families did not map on this locus. So, the "merosin-deficient" CMD can be considered as a peculiar entity within the group of Congenital Muscular Dystrophies.
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PMID:[Congenital muscular dystrophy with merosin deficiency: clinical, histopathological, immunocytochemical and genetic analysis]. 872 91

We report a female infant with non-Fukuyama-type congenital muscular dystrophy with merosin deficiency. She manifested marked hypotonia and muscle weakness from the neonatal period, with an elevated creatine kinase concentration. Her motor developmental milestones were markedly delayed; however, her intellectual development was normal. Although cranial computed tomography (CT) at 3 months of age was normal, subsequent CT at 16 months of age demonstrated diffuse, abnormal white matter lucencies. Muscle biopsy findings at 16 months of age were compatible with those of congenital muscular dystrophy. In addition, no muscle fibers were immunostained by the merosin antibody. The patient died of pneumonia at 23 months of age. These clinical symptoms and CT findings are similar to those described in patients with merosin-negative congenital muscular dystrophy in European countries.
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PMID:Merosin-negative non-Fukuyama-type congenital muscular dystrophy: a case report. 873 5

The laminin alpha 2-chain gene mutations (LAMA2) are responsible for about 50% of the cases of classical congenital muscular dystrophy. These patients form a clinically homogenous group presenting merosin (laminin alpha 2-chain) deficiency in muscle biopsies. The LAMA2 gene has been previously localized on 6q22-23 and the disease locus mapped in a 16 cM interval in 6q2 by homozygosity mapping. In the present report we establish, by haplotyping additional microsatellites markers in 18 consanguineous families, that LAMA2 gene is more centromeric than previously thought: between the flanking markers, D6S407 and D6S1705, distant of 3 cM. In this interval the microsatellite D6S1620 is homozygous for all the patients. The localization of LAMA2 gene was confirmed by radiation hybrid mapping. The 3 new highly informative markers can be very useful for prenatal diagnosis.
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PMID:Readjusting the localization of merosin (laminin alpha 2-chain) deficient congenital muscular dystrophy locus on chromosome 6q2. 874 40

Fukuyama type congenital muscular dystrophy (FCMD) is an autosomal recessive muscular dystrophy associated with an anomaly of the brain. We performed genetic linkage analyses using consanguineous FCMD families and localized the FCMD locus to chromosomes 9q31-33. We further defined the locus within a region of 5 cM and also found strong linkage disequilibrium between FCMD and mfd220. We suspect that the FCMD gene could lie within one megabases of the mfd220 locus located on 9q31. This achievement made prenatal and carrier diagnosis in families carrying FCMD feasible. However, in principle, it is impossible to diagnose whether a patient has FCMD or not, since this is an indirect genetic diagnosis by polymorphisms analysis. It has been discussed whether FCMD and Walker-Warburg syndrome (WWS) belong to the same disease entity or not. We analyzed a family in which 3 siblings were affected with either FCMD or WWS. The results suggested that both FCMD and WWS siblings shared the identical combination of mutations on either allele of the FCMD locus. Some WWS cases could be caused by mutations in the FCMD gene. A novel clinical entity of merosin-negative CMD was proposed out of classical, non-Fukuyama CMD cases. This condition mapped to 6q2, the merosin gene region. CMD researches are in rapid progress.
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PMID:[Recent progress, genetic diagnosis and its problem on congenital muscular dystrophies (Fukuyama and non-Fukuyama types)]. 875 16

The spectacular progress concerning dystrophin and its pathology, the dystrophinopathies, has led to a somewhat arbitrarily separated heterogeneous group of nondystrophinopathic muscular dystrophies that currently comprise the Emery-Dreifuss type, the nosologically heterogeneous autosomal-recessive limb-girdle muscular dystrophy, the severe childhood autosomal-recessive muscular dystrophy, the merosin-positive and -negative congenital muscular dystrophies, the autosomal-recessive distal muscular dystrophy of Miyoshi, the facio-scapulo-humeral muscular dystrophy, and myotonic dystrophy, both the adult and neonatal variants. Deficiencies of adhalin in a particular form of limb-girdle muscular dystrophy, and of merosin in a particular form of congenital muscular dystrophy as well as the newly discovered principle of abnormal tri-nucleotide repeats in myotonic dystrophy are evidence of progress that has also amplified the notion of the dystrophinopathies that the protein-deficient muscular dystrophies can now be considered examples of contributions of the dystrophin-glycoprotein complex across the muscle fiber plasma membrane.
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PMID:Nondystrophinopathic muscular dystrophies including myotonic dystrophy. 879 45

"Classic" congenital muscular dystrophy is a heterogeneous group of disorders, characterized by early-onset muscle weakness and hypotonia, absence of overt cerebral or ocular symptoms, and muscle pathology consistent with a dystrophic process. A subset of patients with congenital muscular dystrophy have recently been found to be deficient in the extracellular matrix protein merosin. Consequently, we reviewed the clinical, pathologic, and immunohistochemical features of 12 patients (six males and six females) with classic congenital muscular dystrophy who have been seen at the Children's Hospital, Boston, over the past 15 years. There was marked clinical heterogeneity within this patient population, with age of independent ambulation ranging from 13 months to 6 years. Immunocytochemical analysis using antibodies to merosin, dystrophin, 43-kDa dystroglycan, adhalin, and laminin was normal in 11 of 12 patients. One patient had markedly abnormal staining for merosin; the majority of fibers were negative, although occasional fibers demonstrated patchy staining. Immunoblot analysis in this patient demonstrated markedly reduced levels of merosin (< 10% compared to controls and other patient), of apparently normal size. Clinically, this patient could be differentiated from the others by a marked elevation of serum creatine kinase (> 1000 U/L) and the presence of early white-matter changes on magnetic resonance imaging. The results of this study support the observation that abnormalities of merosin are present in a subgroup of patients with classic congenital muscular dystrophy. Although marked elevation of serum creatine kinase and white-matter changes on magnetic resonance imaging may serve to distinguish these patients from other patients with congenital muscular dystrophy, there remains a large proportion of patients in whom the underlying pathogenesis remains to be elucidated.
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PMID:Congenital muscular dystrophy associated with merosin deficiency. 880 18

Laminin (laminin-1; alpha 1-beta 1-gamma 1) is known to promote myoblast proliferation, fusion, and myotube formation. Merosin (laminin-2 and -4; alpha 2-beta 1/beta 2-gamma 1) is the predominant laminin variant in skeletal muscle basement membranes; genetic defects affecting its structure or expression are the causes of some types of congenital muscular dystrophy. However, the precise nature of the functions of merosin in muscle remain unknown. We have developed an in vitro system that exploits human RD and mouse C2C12 myoblastic cell lines and their clonal variants to study the roles of merosin and laminin in myogenesis. In the parental cells, which fuse efficiently to multinucleated myotubes, merosin expression is upregulated as a function of differentiation while laminin expression is downregulated. Cells from fusion-deficient clones do not express either protein, but laminin or merosin added to the culture medium induced their fusion. Clonal variants which fuse, but form unstable myotubes, express laminin but not merosin. Exogenous merosin converted these myotubes to a stable phenotype, while laminin had no effect. Myotube instability was corrected most efficiently by transfection of the merosin-deficient cells with the merosin alpha 2 chain cDNA. Finally, merosin appears to promote myotube stability by preventing apoptosis. Hence, these studies identify novel biological functions for merosin in myoblast fusion and muscle cell survival; furthermore, these explain some of the pathogenic events observed in congenital muscular dystrophy caused by merosin deficiency and provide in vitro models to further investigate the molecular mechanisms of this disease.
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PMID:Merosin and laminin in myogenesis; specific requirement for merosin in myotube stability and survival. 883 Jul 76

Recent research revealed that dystrophin and dystrophin-associated proteins from together with the basal lamina a molecular architecture on the cell membrane. Their functions are not clearly known, but assumed from the structural relationship between the molecular architecture and other cell components. The defect of each of the most components of the architecture has been found to correspond with a muscular dystrophy. In this lecture, muscular dystrophies are classified on the basis of these defects. The first structure with merosin-dystroglycans-dystrophin-actin bridges between the muscle basal lamina and membrane cytoskeleton through sarcolemma, whose defect gives rise to muscular dystrophy, such as merosin negative congental muscular dystrophy. The second structure is called sarcoglycan complex composed of three proteins, and loss of any one of its components results in genetically heterogeneous severe childhood autosomal recessive muscular dystrophy (SCARMD). Duchenne and Becker muscular dystrophies are considered as having compound lesions of these two structures.
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PMID:[Muscular dystrophy and dystrophin and its associated proteins]. 885 Dec 78

The majority (approximately 70%) of cases of childhood and adult onset muscular dystrophies in males, and approximately 10% of dystrophy in girls and women, show underlying primary abnormalities of dystrophin. Approximately 2% of childhood/adult onset muscular dystrophy patients have a primary defect of one of the three sarcoglycan proteins identified to date (alpha, beta, gamma). The finding of a sarcoglycan deficiency in muscle generally does not reflect the primary underlying defect, and thus testing of biopsies for sarcoglycans should be used only after normal dystrophin findings, and in conjunction with gene mutation testing. Approximately 30% of neonatal onset congenital muscular dystrophy has been shown to be due alpha 2-laminin (merosin) deficiency. alpha 2-laminin is a component of the myofiber basal lamina, and this protein interacts with the dystrophin-based membrane cytoskeleton. Due to the similar clinical and histopathological features of the different etiologies of muscular dystrophies, molecular testing of peripheral blood DNA and muscle biopsy protein are a critical part of the clinical work-up of dystrophy patients. Many patients carrying a Becker dystrophy or limb-girdle dystrophy diagnosis should be re-evaluated with molecular tests to provide accurate genetic counseling to their families.
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PMID:Clinical and histopathological features of abnormalities of the dystrophin-based membrane cytoskeleton. 886 47

We report clinical, EEG and neuroimaging findings of three patients in two Italian families with merosin-negative congenital muscular dystrophy (CMD), drug-resistant occipital epilepsy, diffuse persistent cerebral white matter changes and focal cortical dysplasia. Clinical and epilepsy histories, EEG and neuroimaging findings were very similar in all patients. Seizures started in childhood and mainly consisted of periodic spasms, a particular type of partial seizure characterized by clusters of epileptic spasms. The motor expression of the spasms was very mild so that they had been frequently missed or misinterpreted as non-convulsive generalized absence seizures. Interictal EEG showed occipital spike-waves and bilateral synchronous slow spike-wave discharges. Ictal EEG showed prolonged periodic sequences of slow waves with associated fast rhythm complexes, characteristic of periodic spasms. Two patients had normal intelligence, one patient presented moderate mental retardation. Focal cortical dysplasia in the posterior areas of the brain, in addition to marked diffuse white matter alterations, was detected in the magnetic resonance images of all patients. Findings in these patients indicate that in merosin-negative CMD brain involvement can include cortical dysplasia, in addition to white matter changes. In such cases the brain damage can lead to a childhood-onset localization-related symptomatic occipital epilepsy. Epileptic seizures and cortical dysplasia can be, however, difficult to detect in CMD. The clinical semiology of epileptic seizures may in fact be modified because of muscular weakness. This implies that epilepsy may be misdiagnosed or even missed and EEG-polymyographic recordings may be necessary to identify it. Similarly, cortical dysplasia may be very localized and visible by neuroimaging only if it is carefully investigated on the basis of epileptological and EEG-polymyographic findings.
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PMID:Merosin-negative congenital muscular dystrophy, occipital epilepsy with periodic spasms and focal cortical dysplasia. Report of three Italian cases in two families. 887 53


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