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

Astrocytes in the cerebrum and medulla oblongata of cases of Fukuyama type congenital muscular dystrophy were examined by immunohistochemistry of oxidative modification products and free-radical scavenging enzymes because abnormal glia limitans formed by astrocytic end feet is considered to be involved in the genesis of brain lesions of Fukuywama type congenital muscular dystrophy. The study was performed on two fetal cases of Fukuyama type congenital muscular dystrophy of 18 and 20 weeks' gestation and seven patients with Fukuyama type congenital muscular dystrophy ranging in age from 2 to 27 years. Eight age-matched control cases were used. Polymerase chain reaction (PCR) was performed to ascertain the gene phenotype of two child cases, in which prenatal gene analysis was not performed. Astrocytes, especially layer I astrocytes, of postnatal cases of Fukuyama type congenital muscular dystrophy were weakly positivefor Nepsilon-(carboxymethyl)lysine and argpyrimidine, suggesting that they were sensitive to oxidative stress, and the accumulation may be related to the abnormal glia limitans. Secondary increase of manganese (Mn) superoxide dismutase against the increase of free radicals was considered in patients with Fukuyama type congenital muscular dystrophy more than 14 years old considered to be homozygous for founder haplotype: homozygosity was suggested by PCR in two cases. In contrast, expression of Mn superoxide dismutase was decreased in 2- and 6-year-old children with Fukuyama type congenital muscular dystrophy that were heterozygous. Moreover, accumulation of argpyrimidine was exclusively found in astrocytes of the 2-year-old child that exhibited severe brain lesions. Function of astrocytes might be impaired or immature in severe or heterozygous cases. These results may confirm that astrocytes play an important role in the etiology of the brain lesion.
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PMID:Oxidative stress in the brain of Fukuyama type congenital muscular dystrophy: immunohistochemical study on astrocytes. 1258 16

Muscle-eye-brain disease (MEB), an autosomal recessive disorder prevalent in Finland, is characterized by congenital muscular dystrophy, brain malformation and ocular abnormalities. Since the MEB phenotype overlaps substantially with those of Fukuyama-type congenital muscular dystrophy (FCMD) and Walker-Warburg syndrome (WWS), these three diseases are thought to result from a similar pathomechanism. Recently, we showed that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) gene. We describe here the identification of seven novel disease-causing mutations in six of not only non-Finnish Caucasian but also Japanese and Korean patients with suspected MEB, severe FCMD or WWS. Including six previously reported mutations, the 13 disease-causing mutations we have found thus far are dispersed throughout the entire POMGnT1 gene. We also observed a slight correlation between the location of the mutation and clinical severity in the brain: patients with mutations near the 5' terminus of the POMGnT1 coding region show relatively severe brain symptoms such as hydrocephalus, while patients with mutations near the 3' terminus have milder phenotypes. Our results indicate that MEB may exist in population groups outside of Finland, with a worldwide distribution beyond our expectations, and that the clinical spectrum of MEB is broader than recognized previously. These findings emphasize the importance of considering MEB and searching for POMGnT1 mutations in WWS or other congenital muscular dystrophy patients worldwide.
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PMID:Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease. 1258

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome, and muscle-eye-brain disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. FCMD is frequent in Japan, but no FCMD patient with confirmed fukutin gene mutations has been identified in a non-Japanese population. Here, we describe a Turkish CMD patient with severe brain and eye anomalies. Sequence analysis of the patient's DNA identified a homozygous 1bp insertion mutation in exon 5 of the fukutin gene. To our knowledge, this is the first case worldwide in which a fukutin mutation has been found outside the Japanese population. This report emphasizes the importance of considering fukutin mutations for diagnostic purposes outside of Japan.
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PMID:A new mutation of the fukutin gene in a non-Japanese patient. 1260 8

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal-recessive disorders in Japan, is characterized by congenital muscular dystrophy associated with brain malformation due to a defect during neuronal migration. Through positional cloning, we previously identified the gene for FCMD, which encodes the fukutin protein. Here we report that chimeric mice generated using embryonic stem cells targeted for both fukutin alleles develop severe muscular dystrophy, with the selective deficiency of alpha-dystroglycan and its laminin-binding activity. In addition, these mice showed laminar disorganization of the cortical structures in the brain with impaired laminin assembly, focal interhemispheric fusion, and hippocampal and cerebellar dysgenesis. Further, chimeric mice showed anomaly of the lens, loss of laminar structure in the retina, and retinal detachment. These results indicate that fukutin is necessary for the maintenance of muscle integrity, cortical histiogenesis, and normal ocular development and suggest the functional linkage between fukutin and alpha-dystroglycan.
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PMID:Fukutin is required for maintenance of muscle integrity, cortical histiogenesis and normal eye development. 1278 52

Fukuyama-type congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), and muscle-eye-brain (MEB) disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. Through positional cloning, we identified the gene for FCMD and MEB, which encodes the fukutin protein and the protein O-linked mannose beta1, 2-N-acetylglucosaminy ltransferase (POMGnT1), respectively. Recent studies have revealed that posttranslational modification of alpha-dystroglycan is associated with these congenital muscular dystrophies with brain malformations. In this review Fukuyama-type congenital muscular dystrophy (FCMD), other CMDs with brain malformations, and their relation with alpha-dystroglycan are discussed.
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PMID:Fukuyama-type congenital muscular dystrophy (FCMD) and alpha-dystroglycanopathy. 1289 68

Recently, post-translational modification of proteins has been defined as a new area of focus for muscular dystrophy research by the identification of a group of disease genes that encode known or putative glycosylation enzymes. Walker-Warburg Syndrome (WWS) and muscle-eye-brain disease (MEB) are caused by mutations in two genes involved in O-mannosylation, POMT1 and POMGnT1, respectively. Fukuyama muscular dystrophy (FCMD) is due to mutations in fukutin, a putative phospholigand transferase. Congenital muscular dystrophy type 1C and limb girdle muscular dystrophy type 2I are allelic, both being due to mutations in the gene-encoding fukutin-related protein (FKRP). Finally, the causative gene in the myodystrophy (myd) mouse is a putative bifunctional glycosyltransferase (Large). WWS, MEB, FCMD and the myd mouse are also associated with neuronal migration abnormalities (often type II lissencephaly) and ocular or retinal defects. A deficiency in post-translational modification of alpha-dystroglycan is a common feature of all these muscular dystrophies and is thought to involve O-glycosylation pathways. This abnormally modified alpha-dystroglycan is deficient in binding to extracellular matrix ligands, including laminin and agrin. Selective deletion of dystroglycan in the central nervous system (CNS) produces brain abnormalities with striking similarities to WWS, MEB, FCMD and the myd mouse. Thus, impaired dystroglycan function is strongly implicated in these diseases. However, it is unlikely that these five glycosylation enzymes only have a role in glycosylation of alpha-dystroglycan and it is important that other protein targets are identified.
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PMID:Glycosylation defects: a new mechanism for muscular dystrophy? 1292 72

Fukuyama-type congenital muscular dystrophy (FCMD) is characterized by congenital muscular dystrophy in combination with central nervous system (CNS) abnormalities. Differential diagnosis of FCMD from Duchenne and Becker muscular dystrophies (DMD/BMD) or other types of congenital muscular dystrophy is occasionally difficult, because of their phenotypic similarity. The gene (FCMD) responsible for FCMD at 9q31 was isolated in 1998. In Japan, most FCMD-bearing chromosomes (87%) have a 3-kb retrotransposal insertion into the 3'-untranslated region (UTR) of the gene that could be derived from a single ancestral founder. Nine non-founder mutations have been identified in Japanese FCMD patients. Severe phenotype was significantly more frequent in patients who were compound heterozygotes for a point mutation and the founder mutation, than in homozygotes for the founder mutation. We developed a PCR-based diagnostic method for a rapid detection of the retrotransposal insertion mutation. Using this system, we screened 18 FCMD patients, and found 16 homozygotes and two heterozygotes for the insertion. We also evaluated the carrier frequency in the normal Japanese population. Six of 676 persons were recognized as a heterozygous carrier. Furthermore, we found three homozygotes for the FCMD founder mutation among 97 patients who had been said to have probable DMD/BMD without any DMD mutations. On the other hand, there were no FCMD homozygotes but four heterozygous carriers among 335 patients with DMD mutations. The diagnostic method we developed will provide a rapid and reliable diagnosis of FCMD, which can bring important information in genetic counseling, such as the accurate mode of inheritance, recurrence risk and a life expectancy.
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PMID:A rapid diagnostic method for a retrotransposal insertional mutation into the FCMD gene in Japanese patients with Fukuyama congenital muscular dystrophy. 1510 18

A woman aged 59 years with adult-onset progressive myopathy had anti-Golgi (giantin) autoantibody in the serum. Limb-muscle biopsy revealed chronic myopathy with paucity of cellular reactions and reduced immunostaining for alpha-dystroglycan. The similarity of the current patient with cases of hereditary alpha-dystroglycanopathies (Fukuyama-type congenital muscular dystrophy, Walker-Warburg syndrome, muscle-eye-brain disease, congenital muscular dystrophy type 1C, and limb-girdle muscular dystrophy type 2I) suggests that the Golgi apparatus is the target organelle in a subset of myopathies.
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PMID:Progressive myopathy with circulating autoantibody against giantin in the Golgi apparatus. 1515 5

Fukuyama-type congenital muscular dystrophy and congenital muscular dystrophy 1C are congenital muscular dystrophies that commonly display reduced levels of glycosylation of alpha-dystroglycan in skeletal muscle. The genes responsible for these disorders are fukutin and fukutin-related protein (FKRP), respectively. Both gene products are thought to be glycosyltransferases, but their functions have not been established. In this study, we determined their subcellular localizations in cultured skeletal myocytes. FKRP localizes in rough endoplasmic reticulum, while fukutin localizes in the cis-Golgi compartment. FKRP was also localized in rough endoplasmic reticulum in skeletal muscle biopsy sample. Our data suggest that fukutin and FKRP may be involved at different steps in O-mannosylglycan synthesis of alpha-dystroglycan, and FKRP is most likely involved in the initial step in this synthesis.
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PMID:Subcellular localization of fukutin and fukutin-related protein in muscle cells. 1521 46

Hypoglycosylation of alpha-dystroglycan (alpha-DG) has been identified in several human diseases associated with muscular dystrophy and brain malformations, including Fukuyama-type congenital muscular dystrophy (FCMD) caused by mutations in the fukutin gene. Although disruption of the intra-extra membrane linkage in the sarcolemma via the dystroglycan (DG) has been hypothesized as a possible underlying mechanism, little is known about the pathogenesis of brain anomalies in these conditions. In this study, we examined the patterns of expression of fukutin and alpha-DG in developing and adult mouse brains. Antisera against fukutin and alpha-DG identified neurons of the fetal cerebral and cerebellar cortex and the subpial pontine migratory stream. In adult mice, fukutin and alpha-DG were extensively co-expressed in neurons of the cerebral and cerebellar cortex, hippocampus, basal ganglia and olfactory bulb, as well as in the pontine nucleus and the cranial nerve nuclei. These results support the hypothesis that fukutin is involved in the glycosylation process of alpha-DG and that a defect in this process plays an essential role in the pathogenesis of FCMD. Further research into the physiological function of alpha-DG in migrating and mature neurons is required.
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PMID:Co-localization of fukutin and alpha-dystroglycan in the mouse central nervous system. 1535 99


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