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

Asahina, Naoko; Okamoto, Takayuki; Sudo, Akira; Kanazawa, Naomi; Tsujino, Seiichi; Saitoh, Shinji

doi:10.1016/j.braindev.2005.05.004

Cited by 12 publications

(6 citation statements)

References 10 publications

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“…The final AxD diagnosis was possible through results of genetic testing. Despite the fact that R79H amino acid substitution is the most common AxD variant, we did not find any case of another child with the c.236G>A mutation and similar clinical outcome, improvement after treatment of seizures, in the literature [11][12][13][14][15]. There is also lack of reliable phenotype-genotype correlation in other GFAP gene variants.…”

Section: Discussioncontrasting

confidence: 58%

Infantile Alexander disease with late onset infantile spasms and hypsarrhythmia

Paprocka

Rzepka-Migut²,

Rzepka³

et al. 2019

Balkan Journal of Medical Genetics

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Alexander disease (AxD) is a rare autosomal dominant leukodystrophy with three clinical subtypes: infantile, juvenile and adult. Forms differ by age of symptoms occurrence and the clinical presentation. Although recent data suggest considering only two subtypes: type I (infantile onset with lesions extending to the cerebral hemispheres); type II (adult onset with primary involvement of subtentorial structures). Dominant mutations in the glial fibrillary acidic protein (GFAP) gene in AxD cause dysfunction of astrocytes (a type III intermediate filament). The authors discuss the clinical picture of a boy with infantile form of AxD confirmed by the presence of de novo heterozygous mutation c.236G>A in the GFAP gene and without striking symptoms such as macrocephaly and with exceptional late-onset epileptic spasms with hypsarrhyth- mia on electroencephalogram (EEG).

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Section: Discussioncontrasting

confidence: 58%

Infantile Alexander disease with late onset infantile spasms and hypsarrhythmia

Paprocka

Rzepka-Migut²,

Rzepka³

et al. 2019

Balkan Journal of Medical Genetics

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“…28 Because the condition in dogs is morphologically and genetically similar to man, it could be a promising animal model for further elucidating the genotype/phenotype correlation in order to treat or prevent (application of drugs or gene therapy) this disease in man. Although the disorder is quite rare, understanding how astrocyte dysfunction contributes to the phenotype in AxD and how astrocyte function might be restored will also contribute to the studies of more common neurological diseases (such as epilepsy, Alzheimer's, Parkinson's and Huntington's disease) or ageing.…”

Section: Discussionmentioning

confidence: 99%

A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever

Poucke¹,

Martlé²,

Brantegem³

et al. 2015

Eur J Hum Genet

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Alexander disease (AxD) is a fatal neurodegenerative disorder of astrocyte dysfunction in man, for which already a number of causal variants are described, mostly de novo dominant missense variants in the glial fibrillary acidic protein (GFAP). A similar disorder was already phenotypically described in animals but without the identification of causal variants. We diagnosed a Labrador retriever with a juvenile form of AxD based on clinical (tetraparesis with spastic front limbs mimicking 'swimming puppy syndrome') and pathological (the detection of GFAP containing Rosenthal fibers in astrocytes) features. In order to identify a causal variant, the coding sequences of the four detected GFAP transcript variants (orthologues from human transcript variants α, γ, δ/ε and κ) were sequenced. From the five detected variants, a heterozygous c

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“…This disease results from mutations in GFAP, with variations in the age of onset and severity depending on the specific underlying mutation (Asahina et al 2006;Hsiao et al 2005;Johnson 2004;Li et al 2005). Alexander disease differs in significant respects from Tibetan terrier NCL.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal intracellular accumulation of GFAP occurs in another neurodegenerative disorder called Alexander disease (Hsiao et al 2005;L ie ta l2005). This disease results from mutations in GFAP, with variations in the age of onset and severity depending on the specific underlying mutation (Asahina et al 2006;Hsiao et al 2005;Johnson 2004;L ie ta l2005). Alexander disease differs in significant respects from Tibetan terrier NCL.…”

Section: Discussionmentioning

confidence: 99%

Accumulation of glial fibrillary acidic protein and histone H4 in brain storage bodies of Tibetan terriers with hereditary neuronal ceroid lipofuscinosis

Katz

Sanders

Mooney

et al. 2007

J of Inher Metab Disea

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Summary The neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative diseases characterized by massive accumulation of autofluorescent storage bodies in neurons and other cells. A late‐onset form of NCL occurs in Tibetan terrier dogs. Gel electrophoretic analyses of isolated storage body proteins from brains of affected dogs indicated that a protein of approximately 50 kDa was consistently prominent and a 16 kDa component was present in some brain storage body preparations. Mass spectral analysis identified the 50 kDa protein as glial fibrillary acidic protein (GFAP), isoform 2. GFAP identification was supported by immunoblot and immunohistochemical analyses. Histone H4 was the major protein in the 16 kDa component. Specific accumulation of GFAP and histone H4 in storage bodies has not been previously reported for any of the NCLs. Tibetan terrier NCL may be the canine correlate of one of the human adult‐onset NCLs for which the genetic bases and storage body compositions have not yet been determined.

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

Cited by 12 publications

References 10 publications

Infantile Alexander disease with late onset infantile spasms and hypsarrhythmia

Infantile Alexander disease with late onset infantile spasms and hypsarrhythmia

A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever

Accumulation of glial fibrillary acidic protein and histone H4 in brain storage bodies of Tibetan terriers with hereditary neuronal ceroid lipofuscinosis

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