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

9 Citations (Scopus)

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

Fingerprint

Cerebellar Ataxia
Ataxia
Mutation
Genes
Genetic Heterogeneity
Tremor
Computational Biology
Autoantibodies
metabotropic glutamate receptor type 1
Exons
Learning
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

The metabotropic glutamate receptor 1, GRM1 : Evaluation as a candidate gene for inherited forms of cerebellar ataxia. / Rossi, Pia Irene Anna; Vaccari, Carlotta Maria; Terracciano, Alessandra; Doria-Lamba, Laura; Facchinetti, Sabrina; Priolo, Manuela; Ayuso, Carmen; De Jorge, Laura; Gimelli, Stefania; Santorelli, Filippo Maria; Ravazzolo, Roberto; Puliti, Aldamaria.

In: Journal of Neurology, Vol. 257, No. 4, 04.2010, p. 598-602.

Research output: Contribution to journalArticle

Rossi, PIA, Vaccari, CM, Terracciano, A, Doria-Lamba, L, Facchinetti, S, Priolo, M, Ayuso, C, De Jorge, L, Gimelli, S, Santorelli, FM, 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, vol. 257, no. 4, pp. 598-602. https://doi.org/10.1007/s00415-009-5380-3
Rossi, Pia Irene Anna ; Vaccari, Carlotta Maria ; Terracciano, Alessandra ; Doria-Lamba, Laura ; Facchinetti, Sabrina ; Priolo, Manuela ; Ayuso, Carmen ; De Jorge, Laura ; Gimelli, Stefania ; Santorelli, Filippo Maria ; Ravazzolo, Roberto ; Puliti, Aldamaria. / The metabotropic glutamate receptor 1, GRM1 : Evaluation as a candidate gene for inherited forms of cerebellar ataxia. In: Journal of Neurology. 2010 ; Vol. 257, No. 4. pp. 598-602.
@article{23f83e4c9c3b4a66ab58401e4729511d,
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.",
keywords = "Crv4 Mouse model, GRM1, Impaired cerebellar coordination, Inherited ataxia, MGlu1 receptor",
author = "Rossi, {Pia Irene Anna} and Vaccari, {Carlotta Maria} and Alessandra Terracciano and Laura Doria-Lamba and Sabrina Facchinetti and Manuela Priolo and Carmen Ayuso and {De Jorge}, Laura and Stefania Gimelli and Santorelli, {Filippo Maria} and Roberto Ravazzolo and Aldamaria Puliti",
year = "2010",
month = "4",
doi = "10.1007/s00415-009-5380-3",
language = "English",
volume = "257",
pages = "598--602",
journal = "Journal of Neurology",
issn = "0340-5354",
publisher = "Dr. Dietrich Steinkopff Verlag GmbH and Co. KG",
number = "4",

}

TY - JOUR

T1 - The metabotropic glutamate receptor 1, GRM1

T2 - Evaluation as a candidate gene for inherited forms of cerebellar ataxia

AU - Rossi, Pia Irene Anna

AU - Vaccari, Carlotta Maria

AU - Terracciano, Alessandra

AU - Doria-Lamba, Laura

AU - Facchinetti, Sabrina

AU - Priolo, Manuela

AU - Ayuso, Carmen

AU - De Jorge, Laura

AU - Gimelli, Stefania

AU - Santorelli, Filippo Maria

AU - Ravazzolo, Roberto

AU - Puliti, Aldamaria

PY - 2010/4

Y1 - 2010/4

N2 - 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.

AB - 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.

KW - Crv4 Mouse model

KW - GRM1

KW - Impaired cerebellar coordination

KW - Inherited ataxia

KW - MGlu1 receptor

UR - http://www.scopus.com/inward/record.url?scp=77951254605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951254605&partnerID=8YFLogxK

U2 - 10.1007/s00415-009-5380-3

DO - 10.1007/s00415-009-5380-3

M3 - Article

C2 - 19924463

AN - SCOPUS:77951254605

VL - 257

SP - 598

EP - 602

JO - Journal of Neurology

JF - Journal of Neurology

SN - 0340-5354

IS - 4

ER -