Hereditary ataxia with onset in adulthood

Gene: STUB1

The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 2:30 p.m. | Last Modified: 1 Feb 2023, 2:30 p.m.

Panel Version: 3.10

Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous STUB1 variants have been reported in both Autosomal recessive spinocerebellar ataxia type 16, OMIM:615768 and Spinocerebellar ataxia 48, OMIM:618093.
PMIDs 34906452; 35493319 report digenic occurrence of heterozygous STUB1 variants, with TBP_CAG expansions of 41-46. They question the validy of Spinocerebellar ataxia 48 (OMIM:618093) as a condition and whether it should be included into Spinocerebellar ataxia 17 (OMIM:607136).

Created: 13 Sep 2022, 11:38 a.m. | Last Modified: 13 Sep 2022, 11:38 a.m.

Panel Version: 2.162

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Green List (high evidence)

Updated inheritance from biallelic to both monoallelic and biallelic following additional reports. Also emerging evidence of digenic interaction with TBP (SCA17) 'intermediate' CAG expansions.

Created: 1 Sep 2022, 7:32 a.m. | Last Modified: 1 Sep 2022, 7:32 a.m.

Panel Version: 2.158

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cerebellar Ataxia; Dementia

Publications

• 32713943, 33564152, 35493319, 34906452

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

Green List (high evidence)

On Ox and Sheffield panels. SCAR16.

Created: 27 Apr 2019, 7:39 p.m.

I don't know

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.

Green List (high evidence)

Multiple reports in the literature for recessive variant. Note that a single family has been reported in lit with apparent AD inheritance of a final exon truncating variant (PMID 30381368), also some evidence in our own patient cohort of heterozygous variants segregating with disease. Should consider reporting heterozygous variants

Created: 15 Apr 2019, 10:06 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Autosomal recessive spinocerebellar ataxia type 16, 615768

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