Neuronal expression of the fukutin gene

Sasaki, Junko; Ishikawa, Kinya; Kobayashi, Kenzo; Kondo-Iida, Eri; Fukayama, Masahisa; Mizusawa, Hidehiro; Takashima, Sachio; Sakakihara, Yoichi; Nakamura, Yusuke; Toda, Tatsushi

doi:10.1093/hmg/9.20.3083

Cited by 32 publications

(16 citation statements)

References 26 publications

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“…Thus, fukutin appears also to play a role in neuronal migration. Consistent with this, in situ hybridisation showed fukutin mRNA to be expressed in the cell body of neuronal cell lineages, but not in glial cells, within the developing human cerebrum and cerebellum [33]. Western blotting and immunohistochemistry using a polyclonal antibody raised against fukutin peptides agrees with the in situ hybridisation data, with the protein showing primarily neuronal expression in prenatal human brain [34].…”

Section: Fukuyama-type Congenital Muscular Dystrophy Fcmdsupporting

confidence: 73%

Glycosylation defects in inherited muscle disease

Hewitt

Grewal

2003

CMLS, Cell. Mol. Life Sci.

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The gene mutated in the myodystrophy mouse, a model of muscular dystrophy, encodes a putative glycosyltransferase, Large. Mutations in genes encoding proteins thought to be involved in glycosylation have now been identified in six human forms of muscular dystrophy. Hereditary inclusion body myopathy and Nonaka myopathy result from defects in sialic acid production. Two forms of congenital muscular dystrophy, Fukuyama-type and MDC1C, result from mutations in members of the fukutin family. MDC1C and limb girdle muscular dystrophy type 2I are allelic, as they are both associated with mutations in the FKRP gene. Mutations in POMGnT, which encodes an enzyme involved in the synthesis of O-mannosyl glycans, result in muscle-eye-brain disease--another congenital form of muscular dystrophy. Abnormal alpha-dystroglycan has been reported in the myodystrophy mouse, and in the congenital and limb girdle muscular dystrophies. Recent data have shown that there is altered glycosylation of the protein and that this reduces its ability to bind to extracellular matrix ligands such as laminin and agrin.

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Section: Fukuyama-type Congenital Muscular Dystrophy Fcmdsupporting

confidence: 73%

Glycosylation defects in inherited muscle disease

Hewitt

Grewal

2003

CMLS, Cell. Mol. Life Sci.

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“…Northern blot analysis showed a ubiquitous expression of fukutin, both in fetal and adult human tissues [Kobayashi et al, 1998]. In situ hybridization in human brain showed fukutin expression in migrating neurons and Cajal-Retzius cells, adult cortical neurons, hippocampal pyramidal cells, and Purkinje cells [Sasaki et al, 2000a]. By immunohistochemistry studies, fukutin was localized in the developing human brain to the Cajal-Retzius cells, the subpial granular layer, the neuropil of the marginal zone, the cortical plate neurons, and the ventricular neuroepithelium.…”

Section: Fukuyama Congenital Muscular Dystrophymentioning

confidence: 99%

Epilepsy and genetic malformations of the cerebral cortex

Guerrini

Carrozzo²

2001

Am. J. Med. Genet.

188

181

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Malformations of the cerebral cortex are an important cause of developmental disabilities and epilepsy. Here we review those malformations for which a genetic basis has been elucidated or is suspected and the types of associated epilepsy. Schizencephaly (cleft brain) has a wide anatomo-clinical spectrum, including partial epilepsy in most patients. Familial occurrence is rare. Heterozygous mutations in the EMX2 gene were reported in 13 patients. X-linked bilateral periventricular nodular heterotopia (BPNH) consists of typical BPNH with epilepsy in females and prenatal lethality in males. About 88% of patients have partial epilepsy. Filamin A mutations, all leading to a truncated protein, have been reported in three families and in sporadic patients. The most frequent forms of lissencephaly (agyria-pachygyria) are caused by mutations of LIS1. XLIS mutations cause classical lissencephaly in hemizygous males and subcortical band heterotopia (SBH) in heterozygous females. The thickness of the heterotopic band and the degree of pachygyria correlate with the likelihood of developing Lennox-Gastaut syndrome. Mutations of the coding region of XLIS were found in all reported pedigrees and in 38-91% of sporadic female patients with SBH. With few exceptions, children with LIS1 mutations have isolated lissencephaly, with severe developmental delay and infantile spasms. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe developmental delay, seizures, and hypotonia has been associated with mutations of the reelin gene. Fukuyama congenital muscular dystrophy is due to mutations of the fukutin gene and is accompanied by polymicrogyria. Febrile seizures and epilepsy with generalized tonic-convulsions appear in about 50% of children but are usually not severe. Tuberous sclerosis (TS) is caused by mutations in at least two genes, TSC1 and TSC2; 75% of cases are sporadic; 60% of patients have epilepsy, manifested in 50% of them as infantile spasms. TSC1 mutations seem to cause a milder disease with fewer cortical tubers and lower frequency of seizures. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria had familial occurrence on several occasions. Genetic heterogeneity is likely, including autosomal recessive, X-linked dominant, X-linked recessive inheritance, and association with 22q11.2 deletions. About 65% of patients have severe epilepsy, often Lennox-Gastaut syndrome.

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“…Although expression of fukutin has been reported in neurons of the adult mouse cerebellum, 55 it is still unclear whether fukutin is strongly expressed in mature neurons of the human CNS; some reports suggest strong expression 56 and others do not. 46,57 These contradictory findings may be derived from the difference between humans and experimental animals, or from differences in experimental procedure including the probes and antibodies used.…”

Section: Predicted Functions Of Fukutinmentioning

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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Neuronal expression of the fukutin gene

Cited by 32 publications

References 26 publications

Glycosylation defects in inherited muscle disease

Glycosylation defects in inherited muscle disease

Epilepsy and genetic malformations of the cerebral cortex

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

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