Hereditary Neuropathy_CMT - isolated
Gene: WARSEnsemblGeneIds (GRCh38): ENSG00000140105
EnsemblGeneIds (GRCh37): ENSG00000140105
OMIM: 191050, Gene2Phenotype
WARS is in 5 panels
4 reviews
Sangavi Sivagnanasundram (Melbourne Health)
WARS1 - Approved new HGNC gene name (HGNC:12729)
Classified as LIMITED by ClinGen Expert Panel - https://search.clinicalgenome.org/CCID:006533
"Based on the curated evidence, we classify the gene-disease relationship of WARS1 and autosomal dominant motor neuropathy as limited, but with the advice to include it on panels."Created: 9 Apr 2024, 1:10 a.m. | Last Modified: 9 Apr 2024, 1:10 a.m.
Panel Version: 1.39
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
distal hereditary motor neuropathy MONDO:0018894
Anna Ritchie (Victorian Clinical Genetics Services)
Seven affected individuals from four families with biallelic variants, showing varying severities of developmental delay, intellectual disability and microcephaly. Hearing impairment and, as well as brain anomalies, skeletal system, movement/gait, and behaviour were variable features.Created: 4 Aug 2022, 6:52 a.m. | Last Modified: 4 Aug 2022, 6:52 a.m.
Panel Version: 1.213
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Neurodevelopmental disorder (MONDO:0700092), WARS-related
Publications
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
ClinGen curation:
In 2017, three families, two Taiwanese and one Belgian, were shown to carry the same heterozygous His257Arg missense variant in WARS1 co-segregating with a juvenile onset distal motor neuropathy phenotype (PMID: 28369220). The authors show evidence of a dominant-negative effect of the His257Arg mutation capable of dimerizing with the wild-type protein and impairing the overall aminoacylation function. When transfected into neuronal-like cells, an effect on neurite length was also observed. Two other WARS1 missense variants have been linked with this consistent juvenile onset HMN phenotype since then (PMID: 31321409). In these two families, significant segregation or de novo inheritance was shown, but functional evidence was absent. The phenotype in all five published WARS1 families is very consistent, a juvenile onset motor neuropathy phenotype affecting both upper and lower limbs without any sensory involvement.
The panel concludes that the evidence for the pathogenicity of the His257Arg mutation is sufficient to link WARS1 to the motor neuropathy phenotype. More reports will solidify the gene-disease relationship in the future. Based on the curated evidence, we classify the gene-disease relationship of WARS1 and autosomal dominant motor neuropathy as limited, but with the advice to include it on panels.Created: 19 Apr 2024, 4:54 a.m. | Last Modified: 19 Apr 2024, 4:54 a.m.
Panel Version: 1.43
HMN9 is an autosomal dominant neurologic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy affecting both the lower and upper limbs.
At least 5 unrelated families reported.Created: 11 May 2021, 10:45 a.m. | Last Modified: 11 May 2021, 10:45 a.m.
Panel Version: 0.148
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neuronopathy, distal hereditary motor, type IX, MIM# 617721
Publications
Naomi Baker (Victorian Clinical Genetics Services)
14 patients from five families were reported to have WARS-related neuropathy across three publications. Expression studies of mutant demonstrated decreased protein when compared to wild-type.
Sources: LiteratureCreated: 20 Apr 2020, 5:51 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Neuronopathy, distal hereditary motor, type IX (OMIM:617721); juvenile to adult onset (15-23 years); distal wasting; distal weakness; length-dependent motor axonal degeneration
Publications
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Amber
- Royal Melbourne Hospital
- Phenotypes
-
- Neuronopathy, distal hereditary motor, type IX, MIM#617721
- OMIM
- 191050
- Clinvar variants
- Variants in WARS
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: wars has been classified as Amber List (Moderate Evidence).
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: wars has been classified as Green List (High Evidence).
Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Phenotypes for gene: WARS were changed from Neuronopathy, distal hereditary motor, type IX, 617721 to Neuronopathy, distal hereditary motor, type IX, MIM#617721
Set publications
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Publications for gene: WARS were set to
Set mode of inheritance
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Mode of inheritance for gene: WARS was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Created, Added New Source, Set mode of inheritance, Set Phenotypes
Bryony Thompson (Royal Melbourne Hospital)gene: WARS was added gene: WARS was added to Hereditary Neuropathy - isolated_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: WARS was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: WARS were set to Neuronopathy, distal hereditary motor, type IX, 617721