Hereditary ataxia with onset in adulthood
Gene: GRM1The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 4:24 p.m. | Last Modified: 10 Oct 2023, 4:24 p.m.
Panel Version: 4.24
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Comment on mode of inheritance: Should be updated from 'biallelic' to 'both mono- and biallelic' at the next GMS panel review. 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, 4:47 p.m. | Last Modified: 1 Nov 2022, 4:47 p.m.
Panel Version: 2.165
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, 4:42 p.m. | Last Modified: 1 Nov 2022, 4:42 p.m.
Panel Version: 2.163
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia 44, OMIM:617691; Spinocerebellar ataxia, autosomal recessive 13, OMIM:614831
Publications
On Oxford and Sheffield panels. 4 ataxia-related DM in HGMD/OMIM.Created: 27 Apr 2019, 7:39 p.m.
Review and rating submitted by James Polke (Neurogenetics Laboratory, Institute of Neurology, London) on behalf of London North GLH for GMS Neurology specialist test group
Created: 27 Apr 2019, 8:55 p.m.
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group.Created: 15 Apr 2019, 10:21 a.m.
For AR form looks like only a single complex variant (clear LoF) has been identified, seen in the homozygous state amongst five apparently unrelated Roma families. Multiple AD variants reported (and additional ones within our own patient cohort).Created: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Spinocerebellar ataxia 44, 617691, autosomal recessive spinocerebellar ataxia type 13, 614831
Variants in this GENE are reported as part of current diagnostic practice
Tag Q4_22_MOI was removed from gene: GRM1.
Mode of inheritance for gene GRM1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for gene: GRM1 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GRM1 were set to
Tag Q4_22_MOI tag was added to gene: GRM1.
Phenotypes for gene: GRM1 were changed from Spinocerebellar ataxia, autosomal recessive 13; Spinocerebellar ataxia 44, 617691, autosomal recessive spinocerebellar ataxia type 13, 614831 to Spinocerebellar ataxia 44, OMIM:617691; Spinocerebellar ataxia, autosomal recessive 13, OMIM:614831
Source London North GMS was added to GRM1.
Added phenotypes Spinocerebellar ataxia 44, 617691, autosomal recessive spinocerebellar ataxia type 13, 614831 for gene: GRM1
Source NHS GMS was added to GRM1.
Source Wessex and West Midlands GLH was added to GRM1.
Checked panel against panel constituents. Ready to promote to version 1.
gene: GRM1 was added gene: GRM1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Green Mode of inheritance for gene: GRM1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: GRM1 were set to Spinocerebellar ataxia, autosomal recessive 13