Advanced search
1 file | 334.75 KB Add to list

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

Mario Van Poucke (UGent) , Valentine Martlé (UGent) , Leen Van Brantegem (UGent) , Richard Ducatelle (UGent) , Luc Van Ham (UGent) , Sofie Bhatti (UGent) and Luc Peelman (UGent)
Author
Organization
Abstract
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/ɛ and κ) were sequenced. From the five detected variants, a heterozygous c.719G>A nucleotide substitution resulting in a p.Arg240His substitution was considered to be causal, because it is orthologous to the heterozygous de novo dominant c.716G>A (p.Arg239His) hotspot variant in man, proven to cause a severe phenotype. In addition, the variant was not found in 50 unrelated healthy Labrador retrievers. Because the condition in dogs is morphologically similar to man, it could be a promising animal model for further elucidating the genotype/phenotype correlation in order to treat or prevent this disease
Keywords
FIBRILLARY ACIDIC PROTEIN, ROSENTHAL FIBER FORMATION, WEB SERVER, DOG, MYELOENCEPHALOPATHY, ENCEPHALOPATHY, EXPRESSION, MUTATIONS, FORM

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 334.75 KB

Citation

Please use this url to cite or link to this publication:

MLA
Van Poucke, Mario et al. “A Canine Orthologue of the Human GFAP c.716G>A (p.Arg239His) Variant Causes Alexander Disease in a Labrador Retriever.” EUROPEAN JOURNAL OF HUMAN GENETICS 24.6 (2016): 852–856. Print.
APA
Van Poucke, M., Martlé, V., Van Brantegem, L., Ducatelle, R., Van Ham, L., Bhatti, S., & Peelman, L. (2016). A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever. EUROPEAN JOURNAL OF HUMAN GENETICS, 24(6), 852–856.
Chicago author-date
Van Poucke, Mario, Valentine Martlé, Leen Van Brantegem, Richard Ducatelle, Luc Van Ham, Sofie Bhatti, and Luc Peelman. 2016. “A Canine Orthologue of the Human GFAP c.716G>A (p.Arg239His) Variant Causes Alexander Disease in a Labrador Retriever.” European Journal of Human Genetics 24 (6): 852–856.
Chicago author-date (all authors)
Van Poucke, Mario, Valentine Martlé, Leen Van Brantegem, Richard Ducatelle, Luc Van Ham, Sofie Bhatti, and Luc Peelman. 2016. “A Canine Orthologue of the Human GFAP c.716G>A (p.Arg239His) Variant Causes Alexander Disease in a Labrador Retriever.” European Journal of Human Genetics 24 (6): 852–856.
Vancouver
1.
Van Poucke M, Martlé V, Van Brantegem L, Ducatelle R, Van Ham L, Bhatti S, et al. A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever. EUROPEAN JOURNAL OF HUMAN GENETICS. 2016;24(6):852–6.
IEEE
[1]
M. Van Poucke et al., “A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever,” EUROPEAN JOURNAL OF HUMAN GENETICS, vol. 24, no. 6, pp. 852–856, 2016.
@article{7160345,
  abstract     = {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/ɛ and κ) were sequenced. From the five detected variants, a heterozygous c.719G>A nucleotide substitution resulting in a p.Arg240His substitution was considered to be causal, because it is orthologous to the heterozygous de novo dominant c.716G>A (p.Arg239His) hotspot variant in man, proven to cause a severe phenotype. In addition, the variant was not found in 50 unrelated healthy Labrador retrievers. Because the condition in dogs is morphologically similar to man, it could be a promising animal model for further elucidating the genotype/phenotype correlation in order to treat or prevent this disease},
  author       = {Van Poucke, Mario and Martlé, Valentine and Van Brantegem, Leen and Ducatelle, Richard and Van Ham, Luc and Bhatti, Sofie and Peelman, Luc},
  issn         = {1018-4813},
  journal      = {EUROPEAN JOURNAL OF HUMAN GENETICS},
  keywords     = {FIBRILLARY ACIDIC PROTEIN,ROSENTHAL FIBER FORMATION,WEB SERVER,DOG,MYELOENCEPHALOPATHY,ENCEPHALOPATHY,EXPRESSION,MUTATIONS,FORM},
  language     = {eng},
  number       = {6},
  pages        = {852--856},
  title        = {A canine orthologue of the human GFAP c.716G>A (p.Arg239His) variant causes Alexander disease in a Labrador retriever},
  url          = {http://dx.doi.org/10.1038/ejhg.2015.223},
  volume       = {24},
  year         = {2016},
}

Altmetric
View in Altmetric
Web of Science
Times cited: