The Fukuyama congenital muscular dystrophy story

Toda, Tatsushi; Kobayashi, Kenzo; Kondo-Iida, Eri; Sasaki, Junko; Nakamura, Yusuke

doi:10.1016/s0960-8966(99)00109-1

Cited by 86 publications

(44 citation statements)

References 46 publications

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“…In addition, residual POMGnT1 activity has been shown in patients with MEB (Zhang et al, 2003). Whereas most of the FCMD patients carry a 3 kb retrotransposon insertion in the 3Ј non-coding region of the gene encoding fukutin, individuals homozygous for this insertion show a milder phenotype than compound heterozygotes carrying the insertion in combination with a missense or nonsense mutation on the other allele, and patients with homozygous nonsense modifications (Beltran-Valero de Bernabe et al, 2003;Toda et al, 2000). Similarly, deletions in the murine Fukutin and POMT1 genes are lethal, although these embryos survive a few days longer than the Dag1-null mutants (Kurahashi et al, 2005;Takeda et al, 2003;Willer et al, 2004).…”

Section: Perturbation Of ␣ ␣-Dystroglycan Glycosylationmentioning

confidence: 99%

Dystroglycan: from biosynthesis to pathogenesis of human disease

Barresi

Campbell

2006

Journal of Cell Science

527

578

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α- and β-dystroglycan constitute a membrane-spanning complex that connects the extracellular matrix to the cytoskeleton. Although a structural role for dystroglycan had been identified, biochemical and genetic discoveries have recently highlighted the significance of posttranslational processing for dystroglycan function. Glycosylation is the crucial modification that modulates the function of dystroglycan as a receptor for extracellular binding partners. It has become clear that perturbation of dystroglycan glycosylation is the central event in the pathogenesis of several complex disorders, and recent advances suggest that glycosylation could be modulated to ameliorate the pathological features. Our increased understanding of the mechanisms of interaction of dystroglycan with its ligands has become an essential tool in deciphering the biological processes related to the human diseases in which the proteins are implicated.

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Section: Perturbation Of ␣ ␣-Dystroglycan Glycosylationmentioning

confidence: 99%

Dystroglycan: from biosynthesis to pathogenesis of human disease

Barresi

Campbell

2006

Journal of Cell Science

527

578

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“…The most common type is Duchenne muscular dystrophy (DMD) in which the dystrophin gene is mutated and defective. The milder Becker muscular dystrophy (BMD), Fukuyama congenital muscular dystrophy [30], myotoninc dystrophy, and multiple types of limb girdle muscular dystrophy (LGMD) are other important muscular dystrophies [31]. Skeletal muscle in dystrophy patients becomes susceptible to tissue inflammation and atrophy.…”

Section: A Muscular Dystrophy and Related Diseasesmentioning

confidence: 99%

Signal Transduction Pathway through Activin Receptors as a Therapeutic Target of Musculoskeletal Diseases and Cancer

et al. 2008

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Abstract. Activin, myostatin and other members of the TGF-β superfamily signal through a combination of type II and type I receptors, both of which are transmembrane serine/threonine kinases. Activin type II receptors, ActRIIA and ActRIIB, are primary ligand binding receptors for activins, nodal, myostatin and GDF11. ActRIIs also bind a subset of bone morphogenetic proteins (BMPs). Type I receptors that form complexes with ActRIIs are dependent on ligands. In the case of activins and nodal, activin receptor-like kinases 4 and 7 (ALK4 and ALK7) are the authentic type I receptors. Myostatin and GDF11 utilize ALK5, although ALK4 could also be activated by these growth factors. ALK4, 5 and 7 are structurally and functionally similar and activate receptor-regulated Smads for TGF-β, Smad2 and 3. BMPs signal through a combination of three type II receptors, BMPRII, ActRIIA, and ActRIIB and four type I receptors, ALK1, 2, 3, and 6. BMPs activate BMP-specific Smads, Smad1, 5 and 8. Smad proteins undergo multimerization with co-mediator Smad, Smad4, and translocated into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. The signal transduction pathway through activin type II receptors, ActRIIA and ActRIIB, with type I receptors is involved in various human diseases. In this review, we discuss the role of signaling through activin receptors as therapeutic targets of intractable neuromuscular diseases, endocrine disorders and cancers.

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“…Among the congenital muscular dystrophies (CMD), failure of alpha-dystroglycan (a-DG) O-glycosylation is the molecular deficit common to a large group of autosomal recessive ''cerebro-oculomuscular'' diseases, reported under the eponyms of WalkerWarburg syndrome (WWS; MIM] 236670), also called HARD 1/-E (hydrocephalus, agyria, retinal dysplasia, encephalocele) [Dobyns et al, 1989], Fukuyama cerebral and muscular dystrophy (FCMD; MIM] 253800) [Toda et al, 2000] and muscle-eye-brain disease (MEBD; MIM] 253280) [Hayashi et al, 2001; Kano et al, 2002;Santavuori et al, 1989]. Distinction between these diseases is difficult because of their overlapping and heterogeneous clinicopathological signs.…”

Section: Introductionmentioning

confidence: 99%

Molecular heterogeneity in fetal forms of type II lissencephaly

et al. 2007

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Type II lissencephaly (type II LIS) is a group of autosomal recessive congenital muscular dystrophies (CMD) associated with defects in alpha-DG O-glycosylation, which comprises Walker-Warburg syndrome, Fukuyama cerebral and muscular dystrophy, or muscle-eye-brain disease. The most severe forms of these diseases often have a fetal presentation and lead to a pregnancy termination. We report here the first molecular study on fetal type II LIS in a series of 47 fetuses from 41 unrelated families. Sequencing of the different genes known to be involved in alpha-DG O-glycosylation allowed the molecular diagnosis in 22 families: involvement of POMT1 was demonstrated in 32% of cases, whereas POMGNT1 and POMT2 were incriminated in 15% and in 7% of cases, respectively. We found 30 different mutations in these three genes, 25 were described herein for the first time, 15 in POMT1, and five in POMT2 and POMGNT1. Despite sequencing of FKRP, FCMD, and LARGE, no definitive molecular diagnosis could be made for the other half of our cases. Preliminary results concerning genotype-phenotype correlations show that the choice of the first gene sequenced should depend on the clinical severity of the type II LIS; POMT1 and POMT2 for severest clinical picture and POMGNT1 for milder disease. The other genes, FKRP, FCMD, and LARGE, seem not to be implicated in the fetal form of CMD.

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The Fukuyama congenital muscular dystrophy story

Cited by 86 publications

References 46 publications

Dystroglycan: from biosynthesis to pathogenesis of human disease

Dystroglycan: from biosynthesis to pathogenesis of human disease

Signal Transduction Pathway through Activin Receptors as a Therapeutic Target of Musculoskeletal Diseases and Cancer

Molecular heterogeneity in fetal forms of type II lissencephaly

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