title: A homozygous deletion in GRID2 causes a human phenotype with cerebellar ataxia and atrophy.
abstract: GRID2 is a member of the ionotropic glutamate receptor family of excitatory neurotransmitter receptors. GRID2 encodes the glutamate receptor subunit delta-2, selectively expressed in cerebellar Purkinje cells. The phenotype associated with loss of GRID2 function was described only in mice until now, characterized by different degrees of cerebellar ataxia and usually relatively mild abnormalities of the cerebellum. This work describes for the first time the human phenotype associated with homozygous partial deletion of GRID2 in 3 children in one large consanguineous Turkish family. Homozygous deletion of exons 3 and 4 of GRID2 (94 153 589-94 298 037 bp) in the proband and similarly affected cousins, and heterozygous deletions in parental DNA were shown using Affymetrix® 6.0 single-nucleotide polymorphism array, confirmed by real-time polymerase chain reaction. The phenotype includes nystagmus, hypotonia with marked developmental delay in gross motor skills in early infancy followed by a static encephalopathy course with development of cerebellar ataxia, oculomotor apraxia, and pyramidal tract involvement.
authors.affiliation: Department of Pediatric Genetics, Hacettepe University, Ankara, Turkey. geutine@hacettepe.edu.tr
authors.forename: G Eda
authors.initials: GE
authors.lastname: Utine
authors.forename: Göknur
authors.initials: G
authors.lastname: Haliloğlu
authors.forename: Bilge
authors.initials: B
authors.lastname: Salanci
authors.forename: Arda
authors.initials: A
authors.lastname: Çetinkaya
authors.forename: P Özlem
authors.initials: PÖ
authors.lastname: Kiper
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Alanay
authors.forename: Dilek
authors.initials: D
authors.lastname: Aktas
authors.forename: Koray
authors.initials: K
authors.lastname: Boduroğlu
authors.forename: Mehmet
authors.initials: M
authors.lastname: Alikaşifoğlu
mesh_terms: D001284:Atrophy / Q000150:complications / Q000235:genetics; D002524:Cerebellar Ataxia / Q000150:complications / Q000235:genetics*; D002531:Cerebellum / Q000473:pathology*; D002648:Child; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D018450:Disease Progression; D005192:Family Health; D020869:Gene Expression Profiling; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D017470:Receptors, Glutamate / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D017470:Receptors, Glutamate; C107913:glutamate receptor delta 2
keywords: GRID2; cerebellar ataxia; deletion; excitatory neurotransmitter; glutamate; homozygous; intellectual disability