The metabotropic glutamate receptor 1, GRM1: evaluation as a candidate gene for inherited forms of cerebellar ataxia.
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.
Rossi
Pia Irene Anna
PI
Laboratory of Molecular Genetics, G. Gaslini Institute, Largo G. Gaslini 5, 16148, Genoa, Italy.
Vaccari
Carlotta Maria
CM
Terracciano
Alessandra
A
Doria-Lamba
Laura
L
Facchinetti
Sabrina
S
Priolo
Manuela
M
Ayuso
Carmen
C
De Jorge
Laura
L
Gimelli
Stefania
S
Santorelli
Filippo Maria
FM
Ravazzolo
Roberto
R
Puliti
Aldamaria
A
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
D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1