The metabotropic glutamate receptor 1, GRM1: Evaluation as a candidate gene for inherited forms of cerebellar ataxia

Pia Irene Anna Rossi, Carlotta Maria Vaccari, Alessandra Terracciano, Laura Doria-Lamba, Sabrina Facchinetti, Manuela Priolo, Carmen Ayuso, Laura De Jorge, Stefania Gimelli, Filippo Maria Santorelli, Roberto Ravazzolo, Aldamaria Puliti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)598-602
Number of pages5
JournalJournal of Neurology
Volume257
Issue number4
DOIs
Publication statusPublished - Apr 2010

Keywords

  • Crv4 Mouse model
  • GRM1
  • Impaired cerebellar coordination
  • Inherited ataxia
  • MGlu1 receptor

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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  • Cite this

    Rossi, P. I. A., Vaccari, C. M., Terracciano, A., Doria-Lamba, L., Facchinetti, S., Priolo, M., Ayuso, C., De Jorge, L., Gimelli, S., Santorelli, F. M., Ravazzolo, R., & Puliti, A. (2010). The metabotropic glutamate receptor 1, GRM1: Evaluation as a candidate gene for inherited forms of cerebellar ataxia. Journal of Neurology, 257(4), 598-602. https://doi.org/10.1007/s00415-009-5380-3