Hereditary ataxia

Gene: GRM1

Green List (high evidence)

Comment on mode of inheritance: Updated from 'biallelic' to 'both mono- and biallelic'. At least two unrelated cases in literature characterised by AD adult-onset ataxia and supported by functional data, plus additional patients mentioned in Tracy Lester patient cohort.

Created: 1 Nov 2022, 4:48 p.m. | Last Modified: 1 Nov 2022, 4:48 p.m.

Panel Version: 1.311

Pathogenic variants in GRM1 have been reported in at least 4 unrelated cases with AR disease (PMID: 22901947; 26308914; 31319223; 36140834) and in 3 unrelated cases with AD disease (PMID: 28886343) - not including additional cases in internal patient cohort mentioned in previous review by Tracy Lester.

Both MOIs are listed in OMIM (MIM# 617691 and MIM# 614831) but only recessive GRM1-related congenital cerebellar ataxia is currently included in G2P.

Biallelic disease is associated with earlier-onset and ID, although some adult patients are reported albeit without indication of the age of onset. On the other hand, the dominant form is a less severe phenotype mainly comprising adult-onset cerebellar ataxia and no cognitive impairment. One juvenile case (presenting ataxic gait and ID) associated with a heterozygous variant was also reported in the same paper but this is not yet sufficient to test heterozygous variants on childhood-onset panel as this may pose a risk of detecting carrier status for an adult-onset condition.

Created: 1 Nov 2022, 4:48 p.m. | Last Modified: 1 Nov 2022, 4:48 p.m.

Panel Version: 1.310

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia 44, OMIM:617691; Spinocerebellar ataxia, autosomal recessive 13, OMIM:614831

Publications

• 22901947
• 26308914
• 31319223
• 36140834
• 28886343

Comment on list classification: Evidence from expert reviewer and OMIM

Created: 4 Feb 2016, 2:09 p.m.

Green List (high evidence)

Fine. Good evidence in lit. Mode of inheritance: AR

Created: 24 Nov 2015, 4:57 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia, autosomal recessive 13

Variants in this GENE are reported as part of current diagnostic practice