title: The metabotropic glutamate receptor 1, GRM1: evaluation as a candidate gene for inherited forms of cerebellar ataxia.
abstract: The metabotropic glutamate (mGlu) 1 receptor, coded by the GRM1 gene, is involved in synaptic activities, learning and neuroprotection. Eleven different mouse Grm1 mutations, either induced or spontaneously occurring, have been reported, including one from our group. All the mutations result in a complex phenotype with ataxia and intention tremor in mice. Moreover, autoantibodies against mGlu1 receptor have been associated with paraneoplastic cerebellar ataxia in humans. In spite of the large clinical and genetic heterogeneity displayed by the inherited forms of cerebellar ataxia, forms remain with a yet unknown molecular definition. With the evidence coming out from mouse models and from paraneoplastic ataxia, it seems that GRM1 represents a good candidate gene for early-onset ataxia forms, though no GRM1 mutations have thus far been looked for. The aim of this study was to investigate the possible involvement of GRM1 in early-onset or familial forms of ataxia. We searched for gene mutations in a panel of patients with early-onset ataxia as yet molecularly undefined. No causative mutations were found, though we detected synonymous variants in the exons and changes in flanking intronic sequences which are unlikely to alter correct splicing upon bioinformatics prediction. As for other known forms of inherited ataxias, absence of mutations in GRM1 seems to suggest a relatively low frequency in cerebellar ataxias.
authors.affiliation: Laboratory of Molecular Genetics, G. Gaslini Institute, Largo G. Gaslini 5, 16148, Genoa, Italy.
authors.forename: Pia Irene Anna
authors.initials: PI
authors.lastname: Rossi
authors.forename: Carlotta Maria
authors.initials: CM
authors.lastname: Vaccari
authors.forename: Alessandra
authors.initials: A
authors.lastname: Terracciano
authors.forename: Laura
authors.initials: L
authors.lastname: Doria-Lamba
authors.forename: Sabrina
authors.initials: S
authors.lastname: Facchinetti
authors.forename: Manuela
authors.initials: M
authors.lastname: Priolo
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Laura
authors.initials: L
authors.lastname: De Jorge
authors.forename: Stefania
authors.initials: S
authors.lastname: Gimelli
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Aldamaria
authors.initials: A
authors.lastname: Puliti
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002524:Cerebellar Ataxia / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D005060:Europe; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D055815:Young Adult
chemical_list: D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1