Molecular genetic study in Japanese patients with Alexander disease: a novel mutation, R79L

Shiroma, Naohide; Kanazawa, Naomi; Kato, Zenichiro; Shimozawa, Nobuyuki; Imamura, Atsushi; Itô, Masayuki; Ohtani, Kyoichi; Oka, Akira; Wakabayashi, Kazuyo; Iai, Mizue; Sugai, Kenji; Sasaki, Masayuki; Kaga, Makiko; Ohta, Takao; Tsujino, Seiichi

doi:10.1016/s0387-7604(02)00167-5

Cited by 19 publications

(16 citation statements)

References 10 publications

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“…Nevertheless, the distinction between the infantile and juvenile forms is not clear. Mutations in the GFAP gene have recently been identified in AD patients [3], and phenotypic variation between cases has been documented [4][5][6][7][8][9]. However, genotype-phenotype correlations…”

Section: Discussionmentioning

confidence: 99%

“…While diagnosis was previously based on neuropathological findings characterized by the presence of Rosenthal fibers in astrocytes [1], AD can now also be diagnosed without histological confirmation, by characteristic magnetic resonance imaging (MRI) findings [2]. Recently, mutations in the glial fibrillary acidic protein (GFAP) gene were identified in AD patients [3][4][5]. This has facilitated the genetic diagnosis of mild AD patients, and the discovery of different clinical manifestations of AD [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, mutations in the glial fibrillary acidic protein (GFAP) gene were identified in AD patients [3][4][5]. This has facilitated the genetic diagnosis of mild AD patients, and the discovery of different clinical manifestations of AD [4][5][6][7][8][9]. However, genotype-phenotype correlations have yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

“…Exons of the GFAP gene were PCR amplified and sequenced as previously described [5]. A heterozygous G-to-A transition at nucleotide 250 (250G>A) in exon 1 was identified (data not shown).…”

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confidence: 99%

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An infantile–juvenile form of Alexander disease caused by a R79H mutation in GFAP

Asahina

Okamoto

Sudo

et al. 2006

Brain and Development

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Alexander disease is a degenerative white matter disorder due to mutations in the glial fibrillary acidic protein (GFAP) gene. It has been classified into three forms based on the age of onset and severity: an infantile, a juvenile, and an adult form. In a six-yearold patient with a relatively mild form of Alexander disease, we detected a common R79H mutation in GFAP previously only described in the infantile form. These results suggest the need for further studies of the genotype-phenotype correlation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Exons of the GFAP gene were PCR amplified and sequenced as previously described [5]. A heterozygous G-to-A transition at nucleotide 250 (250G>A) in exon 1 was identified (data not shown).…”

mentioning

confidence: 99%

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An infantile–juvenile form of Alexander disease caused by a R79H mutation in GFAP

Asahina

Okamoto

Sudo

et al. 2006

Brain and Development

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“…Clinically, Alexander disease is classified into three subtypes: infantile, juvenile, and adult forms, based on the age at disease onset. Recently, GFAP mutations have been reported in various forms of Alexander disease Aoki et al 2001;Rodriguez et al 2001;Shiroma et al 2001;Gorospe et al 2002;Li et al 2002;Meins et al 2002;Namekawa et al 2002;Probst et al 2003;Sawaishi et al 2002;Shiihara et al 2002;Shiroma et al 2003;Suzuki et al 2004) and we have identified juvenile and adult forms of Alexander disease with three different GFAP mutations: V87G (Okamoto et al 2002), R88C (Nobuhara et al 2004) and R416W (Kinoshita et al 2003). To date, there had been few reports investigating the properties of mutant GFAP (Li et al 2005;Hsiao et al 2005;Perng et al 2006).…”

Section: Introductionmentioning

confidence: 83%

The functional alteration of mutant GFAP depends on the location of the domain: morphological and functional studies using astrocytoma-derived cells

et al. 2007

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To clarify the functional effects of mutant glial fibrillary acidic protein (GFAP), we examined the expression patterns of mutant GFAPs (V87G, R88C, and R416W) in astrocytoma-derived cells and performed migration assay. The morphological change was found in mutant GFAP cells, although the number of changes was small. On migration assay, the migration rate in cells with the V87G or R88C mutation, which are located in the helical rod domain in GFAP, was significantly higher than those of wild-type and R416W. These findings suggest that the functional abnormalities of astrocytes might be induced prior to aggregation of GFAP in Alexander disease and that the functional alteration depends on the location of the domain.

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Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease

Johnson

Salomons

et al. 2005

Annals of Neurology

236

291

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Alexander disease is a progressive, usually fatal neurological disorder defined by the widespread and abundant presence in astrocytes of protein aggregates called Rosenthal fibers. The disease most often occurs in infants younger than 2 years and has been labeled a leukodystrophy because of an accompanying severe myelin deficit in the frontal lobes. Later onset forms have also been recognized based on the presence of abundant Rosenthal fibers. In these cases, clinical signs and pathology can be quite different from the infantile form, raising the question whether they share the same underlying cause. Recently, we and others have found pathogenic, de novo missense mutations in the glial fibrillary acidic protein gene in most infantile patients examined and in a few later onset patients. To obtain further information about the role of glial fibrillary acidic protein mutations in Alexander disease, we analyzed 41 new patients and another 3 previously described clinically, including 18 later onset patients. Our results show that dominant missense glial fibrillary acidic protein mutations account for nearly all forms of this disorder. They also significantly expand the catalog of responsible mutations, verify the value of magnetic resonance imaging diagnosis, indicate an unexpected male predominance for the juvenile form, and provide insights into phenotype-genotype relations.

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Molecular genetic study in Japanese patients with Alexander disease: a novel mutation, R79L

Cited by 19 publications

References 10 publications

An infantile–juvenile form of Alexander disease caused by a R79H mutation in GFAP

An infantile–juvenile form of Alexander disease caused by a R79H mutation in GFAP

The functional alteration of mutant GFAP depends on the location of the domain: morphological and functional studies using astrocytoma-derived cells

Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease

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