Hereditary Neuropathy - complex

Gene: SETX

Green List (high evidence)

SETX (senataxin)
EnsemblGeneIds (GRCh38): ENSG00000107290
EnsemblGeneIds (GRCh37): ENSG00000107290
OMIM: 608465, Gene2Phenotype
SETX is in 13 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Bi-allelic variants are associated with spinocerebellar ataxia with axonal neuropathy-2, a neurodegenerative disorder characterised by juvenile onset of progressive cerebellar ataxia, axonal sensorimotor peripheral neuropathy, and increased serum alpha-fetoprotein (AFP; 104150). Oculomotor apraxia is a common but inconsistent finding, found in about 50% of patients; hence this disorder is sometimes referred to as 'ataxia-oculomotor apraxia-2' (AOA2).

Mono-allelic variants are associated with juvenile ALS, a chronic motor neuron disease characterised by combined upper and lower motor neuron symptoms and signs with onset before age 25 years.
Created: 30 Dec 2020, 5:56 a.m. | Last Modified: 30 Dec 2020, 5:56 a.m.
Panel Version: 0.94

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Amyotrophic lateral sclerosis 4, juvenile MIM# 602433; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 MIM# 606002

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

AD: missense mutations
AR: Null variants. Missense in biallelic form clustering in the N-terminal or helicase domains

Chen 2006: postulated LoF for AR condition but partial GoF for AD since heterozygote carriers of AOA2 are unaffected
Ma 2018/Orban 2007: postulated toxic or partial LoF with missense ALS4 since LoF in AOA2 causes a more widespread pathology
Created: 30 Dec 2020, 5:26 a.m. | Last Modified: 30 Dec 2020, 5:26 a.m.
Panel Version: 0.94

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Amyotrophic lateral sclerosis 4, juvenile MIM# 602433; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 MIM# 606002

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Royal Melbourne Hospital
Phenotypes
  • dHMN/dSMA
  • Amyotrophic lateral sclerosis 4, juvenile MIM# 602433
  • Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
OMIM
608465
Clinvar variants
Variants in SETX
Penetrance
None
Publications
Panels with this gene

History Filter Activity

30 Dec 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: setx has been classified as Green List (High Evidence).

30 Dec 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: SETX were changed from dHMN/dSMA; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 to dHMN/dSMA; Amyotrophic lateral sclerosis 4, juvenile MIM# 602433; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2

30 Dec 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: SETX were set to

30 Dec 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: SETX was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

13 Jan 2020, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: SETX was added gene: SETX was added to Hereditary Neuropathy - complex_RMH. Sources: Royal Melbourne Hospital,Expert Review Green Mode of inheritance for gene: SETX was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: SETX were set to dHMN/dSMA; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2