Adult onset dystonia, chorea or related movement disorder
Gene: SPR

SPR (sepiapterin reductase)
EnsemblGeneIds (GRCh38): ENSG00000116096
EnsemblGeneIds (GRCh37): ENSG00000116096
OMIM: 182125, Gene2Phenotype
SPR is in 16 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Red List (low evidence)

The rating of this gene has been updated to red and the mode of inheritance updated to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 11 Mar 2026, 10:21 a.m. | Last Modified: 11 Mar 2026, 10:21 a.m.

Panel Version: 5.5

Created: 11 Mar 2026, 10:21 a.m.
Last Modified: 11 Mar 2026, 10:21 a.m.
Panel version: 5.5

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: Sepiapterin reductase deficiency typically follows an autosomal recessive pattern of inheritance. Two cases with different heterozygous variants have been reported (PMID: 29147684, 15241655) although with reduced penetrance in the familial cases and mild form of the disorder in the singleton.

Overall additional evidence is required to conclusively make an association with monoallelic variants and therefore suggesting the MOI is also changed from 'Both mono- and biallelic' to 'Biallelic', with a watchlist_moi tag to monitor for more dominant cases.
Created: 13 Mar 2025, 5:01 p.m. | Last Modified: 13 Mar 2025, 5:01 p.m.

Panel Version: 4.6

Signs and symptoms of dopa-responsive dystonia usually appear in infancy or childhood, most commonly around age 6 (PMID: 26131547). Severity of disease can vary and milder symptoms may be overlooked leading to recognition of the disorder in late childhood (PMID: 22522443; 21431957). However, there is no evidence of onset in adulthood.

SPR was classified as Red on the R58 Adult onset neurodegenerative disorder panel following expert review due to the typical age of onset. Therefore, recommending that this gene is downgraded from Green to Red on this panel at the next GMS panel update.
Created: 13 Mar 2025, 4:09 p.m. | Last Modified: 13 Mar 2025, 4:09 p.m.

Panel Version: 4.5

Phenotypes
Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716

Publications

26131547

Created: 13 Mar 2025, 4:09 p.m.
Last Modified: 13 Mar 2025, 4:09 p.m.
Panel version: 4.5

Louise Daugherty (Genomics England Curator)

I don't know

Review and rating submitted by James Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Created: 23 Apr 2019, 1:19 p.m.

Created: 23 Apr 2019, 1:19 p.m.

Panel version: 0.54

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

Created: 23 Apr 2019, 1:13 p.m.

Panel version: 0.53

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Red
NHS GMS
London North GLH

Phenotypes

Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, OMIM:612716

Tags

watchlist_moi

OMIM

182125

Clinvar variants

Variants in SPR

Penetrance

None

Publications

http://www.ncbi.nlm.nih.gov/books/NBK1155/
22522443
15241655

Panels with this gene

History Filter Activity

11 Mar 2026, Gel status: 1

Removed Tag, Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q1_25_ MOI was removed from gene: SPR. Tag Q1_25_ demote_red was removed from gene: SPR. Tag Q1_25_ expert_review was removed from gene: SPR.

11 Mar 2026, Gel status: 1

Added New Source, Set mode of inheritance, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Red was added to SPR. Mode of inheritance for gene SPR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal Rating Changed from Green List (high evidence) to Red List (low evidence)

13 Mar 2025, Gel status: 3