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Adult onset hereditary spastic paraplegia

Gene: UCHL1

Green List (high evidence)
UCHL1 (ubiquitin C-terminal hydrolase L1)
EnsemblGeneIds (GRCh38): ENSG00000154277
EnsemblGeneIds (GRCh37): ENSG00000154277
OMIM: 191342, Gene2Phenotype
UCHL1 is in 10 panels

7 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Created: 4 May 2024, 4:56 p.m. | Last Modified: 4 May 2024, 5:01 p.m.
Panel Version: 4.3

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 4 May 2024, 4:56 p.m.
Last Modified: 4 May 2024, 5:01 p.m.
Panel version: 4.3

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 28 Jul 2023, 11:48 a.m. | Last Modified: 28 Jul 2023, 11:48 a.m.
Panel Version: 3.13
Spasticity was reported in at least six families carrying heterozygous UCHL1 variants (PMID: 35986737, figure 2 & table S5). Overall, the disease onset for Spastic paraplegia 79A, autosomal dominant, OMIM:620221 had a median of 49 years (12-70years).
Created: 28 Jul 2023, 11:38 a.m. | Last Modified: 28 Jul 2023, 11:38 a.m.
Panel Version: 3.12
In addition to previous reports of Spastic paraplegia 79, autosomal recessive (OMIM:615491), PMID: 35986737 reports a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy in cases with heterozygous UCHL1 variants. The variants included 13 heterozygous loss-of-function variants (15 families) and a heterozygous in-frame insertion (3 families). The affected individuals mainly presented with spasticity (24/31), ataxia (28/31), neuropathy (11/21), and optic atrophy (9/17), it was also noted in PMID: 35986737 that the condition onset in dominant cases was median 49 years (12-70 years) and in recessive was 7.5 years (2-10 years).
Created: 17 Jan 2023, 3:19 p.m. | Last Modified: 17 Jan 2023, 3:19 p.m.
Panel Version: 2.4
The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 14 Mar 2022, 1:19 p.m. | Last Modified: 14 Mar 2022, 1:19 p.m.
Panel Version: 1.95

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Created: 14 Mar 2022, 1:19 p.m.
Last Modified: 14 Mar 2022, 1:19 p.m.
Panel version: 3.12

Arina Puzriakova (Genomics England Curator)

I don't know

Tagged for GMS expert review (Q2_21) to seek opinion on whether this gene rating needs to be changed. Ten individuals from four families have been reported with a childhood-onset neurodegenerative disorder and different biallelic variants in this gene. Age of onset ranges from 2 to 10 years, however visual loss appears to be one of the first presenting features in most cases and spasticity becomes apparent later in the clinical course but still mostly within the childhood-adolescence age range (PMIDs: 23359680; 28007905; 29735986; 32656641). Inclusion may be justified to ensure that edge cases may be identified.
Created: 11 May 2021, 10:42 a.m. | Last Modified: 11 May 2021, 10:42 a.m.
Panel Version: 1.17

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spastic paraplegia 79, autosomal recessive, OMIM:615491

Publications

Created: 11 May 2021, 10:42 a.m.
Last Modified: 11 May 2021, 10:42 a.m.
Panel version: 1.17

Zornitza Stark (Australian Genomics)

Red List (low evidence)

Childhood onset.
Created: 22 Sep 2020, 5:28 a.m. | Last Modified: 22 Sep 2020, 5:28 a.m.
Panel Version: 1.7
Created: 22 Sep 2020, 5:28 a.m.
Last Modified: 22 Sep 2020, 5:28 a.m.
Panel version: 1.7

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

I don't know

Three families described. Childhood onset. No adult onset cases described.
Created: 10 May 2019, 11:05 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 10 May 2019, 11:05 a.m.

Panel version: 0.53

Louise Daugherty (Genomics England Curator)

I don't know

Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Created: 21 May 2019, 4:14 p.m.
Review and rating submitted byJames Polke (Neurogenetics Laboratory,Institute of Neurology, London), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:50 p.m.
Created: 25 Apr 2019, 1:37 p.m.

Panel version: 0.148

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

Green List (high evidence)

spasticity, cerebellar ataxia, peripheral neuropathy, and myokymia, consistent with systemic neurodegeneration and deficits at the neuromuscular junction.2x 3 sibs in 2 x unrealated families with SPG79
Created: 25 Apr 2019, 1:22 p.m.

Phenotypes
Spastic paraplegia 79, autosomal recessive, 615491, AR

Created: 25 Apr 2019, 1:22 p.m.

Panel version: 0.5

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Yorkshire and North East GLH
  • NHS GMS
  • London North GLH
Phenotypes
  • Spastic paraplegia 79B, autosomal recessive, OMIM:615491
  • early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209
  • Spastic paraplegia 79A, autosomal dominant, OMIM:620221
OMIM
191342
Clinvar variants
Variants in UCHL1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

4 May 2024, Gel status: 3

Removed Tag, Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green was removed from gene: UCHL1. Tag Q3_23_MOI was removed from gene: UCHL1.

4 May 2024, Gel status: 3

Added New Source, Set mode of inheritance, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to UCHL1. Mode of inheritance for gene UCHL1 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

28 Jul 2023, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: uchl1 has been classified as Amber List (Moderate Evidence).

28 Jul 2023, Gel status: 2

Added Tag, Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_23_promote_green tag was added to gene: UCHL1. Tag Q3_23_MOI tag was added to gene: UCHL1.

28 Jul 2023, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221 to Spastic paraplegia 79B, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221

28 Jul 2023, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209; Spastic paraplegia 79A, autosomal dominant, OMIM:620221

17 Jan 2023, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, OMIM:615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491; early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209

17 Jan 2023, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: UCHL1 were set to 23359680; 28007905; 29735986; 32656641

14 Mar 2022, Gel status: 2

Removed Tag

Ivone Leong (Genomics England Curator)

Tag Q2_21_expert_review was removed from gene: UCHL1.

14 Mar 2022, Gel status: 2

Added New Source, Status Update

Ivone Leong (Genomics England Curator)

Source Expert Review Amber was added to UCHL1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)

11 May 2021, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, 615491, AR to Spastic paraplegia 79, autosomal recessive, OMIM:615491

11 May 2021, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: UCHL1 were set to 29735986; 28007905; 23359680

11 May 2021, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_expert_review tag was added to gene: UCHL1.

13 May 2019, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: UCHL1 were set to

13 May 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to UCHL1.

27 Apr 2019, Gel status: 4

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: UCHL1 was changed from to BIALLELIC, autosomal or pseudoautosomal

25 Apr 2019, Gel status: 3

Added New Source, Set Phenotypes, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to UCHL1. Added phenotypes Spastic paraplegia 79, autosomal recessive, 615491, AR for gene: UCHL1 Rating Changed from Red List (low evidence) to Green List (high evidence)

24 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to UCHL1.

24 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: UCHL1 was added gene: UCHL1 was added to Hereditary spastic paraplegia - adult onset. Sources: London North GLH Mode of inheritance for gene: UCHL1 was set to