Early Ultrastructural Changes in the Central Nervous System in Fukuyama Congenital Muscular Dystrophy

Yamamoto, Tomoko; Shibata, Noriyuki; Kanazawa, Miho; Kobayashi, Makio; Komori, Takashi; Kondo, Eri; Saito, Kayoko; Ōsawa, Makiko

doi:10.3109/01913129709021933

Cited by 21 publications

(16 citation statements)

References 17 publications

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“…This agrees with the fact that children with FCMD show micropolygyria, skeletal muscle atrophy and cardiomyopathy [6]. The precise function of fukutin is speculative, but its absence may cause structural alteration of the basal lamina of the central nervous system [15,32]. E) and anti-b-spectrin (C, F) antibodies.…”

Section: Discussionsupporting

confidence: 75%

“…In the case of the merosin immunoreactivity of FCMD myofibers, decreased immunoreactivity for merosin in the basal lamina of FCMD myofibers has been described [9]. Alterations of the basal lamina of FCMD myofibers at the ultrastructural level have been described [10,32], as well as the apparently normal ultrastructure of the basal lamina of FCMD myofibers [29].…”

Section: Discussionmentioning

confidence: 99%

“…The relative prevalence rate of FCMD compared with Duchenne muscular dystrophy (DMD) is 1:2.1 [6]. FCMD is an autosomal recessive disease affecting not only skeletal muscle, but also the central nervous system [6,15,32]. The gene locus is on chromosome 9q31 [22].…”

Section: Introductionmentioning

confidence: 99%

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Altered aquaporin 4 expression in muscles of Fukuyama-type congenital muscular dystrophy

et al. 2003

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This study was undertaken to investigate the expression of aquaporin 4 (AQP4) in the muscle plasma membrane of children with Fukuyama-type congenital muscular dystrophy (FCMD) at protein and mRNA levels. The biopsied six muscles with FCMD, six histochemically normal muscles and eight disease control muscles were analyzed by means of immunoblots, immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR). Immunoblots showed that the band of FCMD muscle extracts stained with anti-AQP4 antibody was faint in comparison with that of normal muscle extracts. The immunohistochemistry revealed that most of the FCMD myofibers showed negative immunostaining with anti-AQP4 antibody, although the partially positive immunostaining of sporadic FCMD myofibers was noted. The immunoreactivity was positive with anti-dystrophin and anti-beta-spectrin antibodies in almost all FCMD myofibers. The quantitative RT-PCR demonstrated that the AQP4 mRNA level of the FCMD muscles was markedly reduced. On the basis of these findings, we conclude that the expression of AQP4 in FCMD myofibers is reduced and the reduced content of AQP4 mRNA in FCMD muscles may be related to the decreased expression of AQP4 at the muscle plasma membrane of FCMD myofibers.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Altered aquaporin 4 expression in muscles of Fukuyama-type congenital muscular dystrophy

et al. 2003

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“…30 In fetal and adult FCMD cases, this cell structure is abnormal. 31,32 In addition to the defects that can be observed by light microscopy, there are minute defects, up to several micrometers, in the cell membrane and basement membrane (Fig. 3).…”

Section: Cns Lesions In Fetal Fcmd Casesmentioning

confidence: 99%

Expression and localization of fukutin, POMGnT1, and POMT1 in the central nervous system: consideration for functions of fukutin

Yamamoto

Kato

Kawaguchi

et al. 2004

Med Electron Microsc

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Fukuyama-type congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), and Walker-Warburg syndrome (WWS) are congenital muscular dystrophies associated with central nervous system (CNS) lesions, represented by cobblestone lissencephaly and eye anomalies. The glia limitans, formed by astrocytic endfeet and covered with the basement membrane, is disrupted in fetal cases of these diseases. A gene responsible for FCMD is fukutin and that for MEB is protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1). Mutations in protein-O-mannosyltransferase 1 (POMT1) have been found in some WWS cases. POMGnT1 and POMT1 are involved in glycosylation of alpha-dystroglycan, which is one of the components of dystrophin-glycoprotein complex, linking dystrophin and extracellular matrix proteins at the basement membrane. Fukutin seems to have similar functions to those of POMGnT1 and POMT1, but its functions still remain to be clarified. In situ hybridization reveals that fukutin, POMGnT1, and POMT1 are expressed especially in astrocytes. Decrease of glycosylated alpha-dystroglycan has been reported in the skeletal muscle of FCMD, MEB, and WWS. Moreover, decrease of fukutin and glycosylated alpha-dystroglycan is observed in the brain of FCMD cases. Because astrocytes are involved in basement membrane formation at the glia limitans, fukutin, POMGnT1, and POMT1 are considered to relate to the pathogenesis of CNS lesions, and fukutin may be related to glycosylation of alpha-dystroglycan. Fukutin, POMGnT1, and POMT1 are expressed in immature neurons, suggesting they are also involved in neuronal migration itself. POMGnT1 and POMT1 are expressed in many mature neurons, but fukutin is positive in a few mature neurons. FCMD is a rather mild disease among FCMD, MEB, and WWS, and POMGnT1 and POMT1 seems to have more critical roles compared to fukutin in mature neurons.

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“…A 3-kb retrotransposal insertion was detected as the ancestral founder mutation of FCMD. These advances have facilitated the diagnosis of FCMD [Kondo-Iida et al, 1997a;Kondo-Iida et al, 1997b;Nakano et al, 1996;Saito et al, 1998;Yamamoto et al, 1996;Yamamoto et al, 1997a;Yamamoto et al, 1997b].…”

Section: Introductionmentioning

confidence: 99%

Haplotype-Phenotype correlation in Fukuyama congenital muscular dystrophy

et al. 2000

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In typical Fukuyama congenital muscular dystrophy (FCMD), peak motor function is usually only unassisted sitting or sliding on the buttocks, though a few patients are able to walk at some point. However, a few patients have a severe phenotype and never acquire head control. In addition, it is clinically difficult to differentiate this severe FCMD from Walker-Warburg syndrome (WWS) or from muscle-eye-brain disease (MEBD). In order to establish a genotype-phenotype correlation, we performed haplotype analysis using microsatellite markers closest to the FCMD gene (FCMD) in 56 Japanese FCMD families, including 35 families whose children were diagnosed as FCMD with the typical phenotype, 12 families with a mild phenotype, and 9 families with a severe phenotype. Of the 12 propositi with the mild phenotype, 8 could walk and the other 4 could stand with support; 10 cases were homozygous for the ancestral founder (A-F) haplotype whereas the other 2 were heterozygous for the haplotype. In the 9 severe cases, who had never acquired head control or the ability to sit without support, 3 had progressive hydrocephalus, 2 required a shunt operation, and 7 had ophthalmological abnormalities. Haplotype analysis showed that 8 of the 9 cases of the severe phenotype are heterozygous for the A-F haplotype, and the other one homozygous for the haplotype. We confirmed that at least one chromosome in each of the 56 FCMD patients has the A-F haplotype. The rate of heterozygosity for the A-F haplotypes was significantly higher in severe cases than in typical or mild cases (P < 0.005). Severe FCMD patients appeared to be compound heterozygotes for the founder mutation and another mutation. Thus, the present study yielded molecular genetic evidence of a broad clinical spectrum in FCMD.

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Early Ultrastructural Changes in the Central Nervous System in Fukuyama Congenital Muscular Dystrophy

Cited by 21 publications

References 17 publications

Altered aquaporin 4 expression in muscles of Fukuyama-type congenital muscular dystrophy

Altered aquaporin 4 expression in muscles of Fukuyama-type congenital muscular dystrophy

Expression and localization of fukutin, POMGnT1, and POMT1 in the central nervous system: consideration for functions of fukutin

Haplotype-Phenotype correlation in Fukuyama congenital muscular dystrophy

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