Universität zu Köln

Van Schil, Kristof, Meire, Francoise, Karlstetter, Marcus, Bauwens, Miriam, Verdin, Hannah, Coppieters, Frauke ORCID: 0000-0001-7224-0992, Scheiffert, Eva, Van Nechel, Christian, Langmann, Thomas, Deconinck, Nicolas and De Baere, Elfride ORCID: 0000-0002-5609-6895 (2015). Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion. Genet. Med., 17 (4). S. 291 - 300. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0366

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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. Genet Med advance online publication 14 August 2014

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Van Schil, Kristof UNSPECIFIED UNSPECIFIED UNSPECIFIED Meire, Francoise UNSPECIFIED UNSPECIFIED UNSPECIFIED Karlstetter, Marcus UNSPECIFIED UNSPECIFIED UNSPECIFIED Bauwens, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Verdin, Hannah UNSPECIFIED UNSPECIFIED UNSPECIFIED Coppieters, Frauke UNSPECIFIED orcid.org/0000-0001-7224-0992 UNSPECIFIED Scheiffert, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Van Nechel, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Langmann, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Deconinck, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED De Baere, Elfride UNSPECIFIED orcid.org/0000-0002-5609-6895 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-403374
DOI:	10.1038/gim.2014.95
Journal or Publication Title:	Genet. Med.
Volume:	17
Number:	4
Page Range:	S. 291 - 300
Date:	2015
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1530-0366
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DELTA-2 GLUTAMATE-RECEPTOR; TIME QUANTITATIVE PCR; PURKINJE-CELLS; HOT-SPOT; MUTATIONS; GENE; SUBUNIT; GLUTAMATE-RECEPTOR-DELTA-2; EXPRESSION Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40337