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Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion

(2015) GENETICS IN MEDICINE. 17(4). p.291-299
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Abstract
Purpose: The aim of this study was to identify the genetic cause of early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy in a consanguineous family. Methods: An affected 6-month-old child underwent neurological and ophthalmological examinations. Genetic analyses included homozygosity mapping, copy number analysis, conventional polymerase chain reaction, Sanger sequencing, quantitative polymerase chain reaction, and whole-exome sequencing. Expression analysis of GRID2 was performed by quantitative polymerase chain reaction and immunohistochemistry. Results: A homozygous deletion of exon 2 of GRID2 (p.G1y30_Glu-81del) was identified in the proband. GRID2 encodes an ionotropic glutamate receptor known to be selectively expressed in cerebellar Purkinje cells. Here, we demonstrated GRID2 expression in human adult retina and retinal pigment epithelium. In addition, Grid2 expression was demonstrated in different stages of murine retinal development. GRID2 immunostaining was shown in murine and human retina. Whole-exome sequencing in the proband did not provide arguments for other disease-causing mutations, supporting the idea that the phenotype observed represents a single clinical entity. Conclusion: We identified GRID2 as an underlying disease gene of early-onset autosomal recessive cerebellar ataxia with retinal dystrophy, expanding the clinical spectrum of GRID2 deletion mutants. We demonstrated for the first time GRID2 expression and localization in human and murine retina, providing evidence for a novel functional role of GRID2 in the retina.
Keywords
glutamate receptor, autosomal recessive cerebellar ataxia, GRID2, hotfoot, retinal dystrophy, DELTA-2 GLUTAMATE-RECEPTOR, TIME QUANTITATIVE PCR, PURKINJE-CELLS, HOT-SPOT, MUTATIONS, GENE, SUBUNIT, GLUTAMATE-RECEPTOR-DELTA-2, EXPRESSION

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Chicago
Van Schil, Kristof, Françoise Meire, Marcus Karlstetter, Miriam Bauwens, Hannah Verdin, Frauke Coppieters, Eva Scheiffert, et al. 2015. “Early-onset Autosomal Recessive Cerebellar Ataxia Associated with Retinal Dystrophy: New Human Hotfoot Phenotype Caused by Homozygous GRID2 Deletion.” Genetics in Medicine 17 (4): 291–299.
APA
Van Schil, K., Meire, F., Karlstetter, M., Bauwens, M., Verdin, H., Coppieters, F., Scheiffert, E., et al. (2015). Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion. GENETICS IN MEDICINE, 17(4), 291–299.
Vancouver
1.
Van Schil K, Meire F, Karlstetter M, Bauwens M, Verdin H, Coppieters F, et al. Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion. GENETICS IN MEDICINE. 2015;17(4):291–9.
MLA
Van Schil, Kristof, Françoise Meire, Marcus Karlstetter, et al. “Early-onset Autosomal Recessive Cerebellar Ataxia Associated with Retinal Dystrophy: New Human Hotfoot Phenotype Caused by Homozygous GRID2 Deletion.” GENETICS IN MEDICINE 17.4 (2015): 291–299. Print.
@article{5846920,
  abstract     = {Purpose: The aim of this study was to identify the genetic cause of early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy in a consanguineous family. 
Methods: An affected 6-month-old child underwent neurological and ophthalmological examinations. Genetic analyses included homozygosity mapping, copy number analysis, conventional polymerase chain reaction, Sanger sequencing, quantitative polymerase chain reaction, and whole-exome sequencing. Expression analysis of GRID2 was performed by quantitative polymerase chain reaction and immunohistochemistry. 
Results: A homozygous deletion of exon 2 of GRID2 (p.G1y30\_Glu-81del) was identified in the proband. GRID2 encodes an ionotropic glutamate receptor known to be selectively expressed in cerebellar Purkinje cells. Here, we demonstrated GRID2 expression in human adult retina and retinal pigment epithelium. In addition, Grid2 expression was demonstrated in different stages of murine retinal development. GRID2 immunostaining was shown in murine and human retina. Whole-exome sequencing in the proband did not provide arguments for other disease-causing mutations, supporting the idea that the phenotype observed represents a single clinical entity. 
Conclusion: We identified GRID2 as an underlying disease gene of early-onset autosomal recessive cerebellar ataxia with retinal dystrophy, expanding the clinical spectrum of GRID2 deletion mutants. We demonstrated for the first time GRID2 expression and localization in human and murine retina, providing evidence for a novel functional role of GRID2 in the retina.},
  author       = {Van Schil, Kristof and Meire, Fran\c{c}oise and Karlstetter, Marcus and Bauwens, Miriam and Verdin, Hannah and Coppieters, Frauke and Scheiffert, Eva and Van Nechel, Christian and Langmann, Thomas and Deconinck, Nicolas and De Baere, Elfride},
  issn         = {1098-3600},
  journal      = {GENETICS IN MEDICINE},
  keyword      = {glutamate receptor,autosomal recessive cerebellar ataxia,GRID2,hotfoot,retinal dystrophy,DELTA-2 GLUTAMATE-RECEPTOR,TIME QUANTITATIVE PCR,PURKINJE-CELLS,HOT-SPOT,MUTATIONS,GENE,SUBUNIT,GLUTAMATE-RECEPTOR-DELTA-2,EXPRESSION},
  language     = {eng},
  number       = {4},
  pages        = {291--299},
  title        = {Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion},
  url          = {http://dx.doi.org/10.1038/gim.2014.95},
  volume       = {17},
  year         = {2015},
}

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