Adult onset hereditary spastic paraplegia
Gene: UCHL1
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
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
Childhood onset.Created: 22 Sep 2020, 5:28 a.m. | Last Modified: 22 Sep 2020, 5:28 a.m.
Panel Version: 1.7
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.
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 SPG79Created: 25 Apr 2019, 1:22 p.m.
Phenotypes
Spastic paraplegia 79, autosomal recessive, 615491, AR
Gene: uchl1 has been classified as Amber List (Moderate Evidence).
Tag Q3_23_promote_green tag was added to gene: UCHL1. Tag Q3_23_MOI tag was added to gene: UCHL1.
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
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
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
Publications for gene: UCHL1 were set to 23359680; 28007905; 29735986; 32656641
Tag Q2_21_expert_review was removed from gene: UCHL1.
Source Expert Review Amber was added to UCHL1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Phenotypes for gene: UCHL1 were changed from Spastic paraplegia 79, autosomal recessive, 615491, AR to Spastic paraplegia 79, autosomal recessive, OMIM:615491
Publications for gene: UCHL1 were set to 29735986; 28007905; 23359680
Tag Q2_21_expert_review tag was added to gene: UCHL1.
Publications for gene: UCHL1 were set to
Source Yorkshire and North East GLH was added to UCHL1.
Mode of inheritance for gene: UCHL1 was changed from to BIALLELIC, autosomal or pseudoautosomal
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)
Source NHS GMS was added to UCHL1.
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