Hereditary ataxia with onset in adulthood
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, 11:47 a.m. | Last Modified: 28 Jul 2023, 11:47 a.m.
Panel Version: 4.17
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, 3:20 p.m. | Last Modified: 28 Jul 2023, 11:46 a.m.
Panel Version: 4.16
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 9 Mar 2022, 5:26 p.m. | Last Modified: 9 Mar 2022, 5:26 p.m.
Panel Version: 2.144
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
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 ataxia becomes apparent later in the clinical course (PMIDs: 23359680; 28007905; 29735986; 32656641). Inclusion may be justified to ensure that edge cases may be identified.Created: 11 May 2021, 10:31 a.m. | Last Modified: 11 May 2021, 10:36 a.m.
Panel Version: 2.44
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spastic paraplegia 79, autosomal recessive, OMIM:615491
Publications
This is a paediatric onset disorder.Created: 13 Sep 2020, 8 a.m. | Last Modified: 13 Sep 2020, 8 a.m.
Panel Version: 2.9
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Spastic paraplegia 79, autosomal recessive, MIM#615491
Publications
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.
Looks like across the three papers we have sufficient families with functional evidence for some variants. Cerebellar abnormalities a feature in affected individualsCreated: 15 Apr 2019, 10:06 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Autosomal recessive spastic paraplegia 79, 615491
Tag Q3_23_promote_green tag was added to gene: UCHL1. Tag Q3_23_MOI tag was added to gene: UCHL1.
Gene: uchl1 has been classified as Amber List (Moderate Evidence).
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 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 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 Early onset ataxia and optic neuropathy; Autosomal recessive spastic paraplegia 79, 615491 to Spastic paraplegia 79, autosomal recessive, OMIM:615491
Publications for gene: UCHL1 were set to 23359680
Tag Q2_21_expert_review tag was added to gene: UCHL1.
Gene: uchl1 has been classified as Green List (High Evidence).
Added phenotypes Autosomal recessive spastic paraplegia 79, 615491 for gene: UCHL1
Source NHS GMS was added to UCHL1.
Source Wessex and West Midlands GLH was added to UCHL1.
Louise Daugherty: Comment on phenotypes: Implica
gene: UCHL1 was added gene: UCHL1 was added to Hereditary ataxia - adult onset. Sources: Hereditary ataxia v1.148,Expert Review Red Mode of inheritance for gene: UCHL1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: UCHL1 were set to 23359680 Phenotypes for gene: UCHL1 were set to Early onset ataxia and optic neuropathy