Hereditary neuropathy

Gene: SETX

The Q2_22_MOI tag has been added to this gene as the MOI should be changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal, as both Spinocerebellar ataxia, autosomal recessive 1, OMIM:606002;Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433 are relevant to this panel.

Created: 19 Apr 2022, 2:09 p.m. | Last Modified: 19 Apr 2022, 2:09 p.m.

Panel Version: 1.452

Comment on publications: PMID:25802885 - Identifiy one previously reported variant and three novel variants in 4 families. Report the variants found in CMT patients are likely nonpathogenic due to bioinformatics analysis. Report SETX c.7640T>C is a nonpathogenic rare variant;PMID: 25025039 - a likely pathogenic variant in SETX reported in a sporadic case with CMT2 and spasticity. Found with a REEP1 variant, and the authors assume digenic pathogenicity.

Created: 19 Apr 2022, 2:06 p.m. | Last Modified: 19 Apr 2022, 2:06 p.m.

Panel Version: 1.451

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Spinocerebellar ataxia, autosomal recessive 1, OMIM:606002; Amyotrophic lateral sclerosis 4, juvenile, OMIM:602433

Green List (high evidence)

The Neurology Specialist Test Group agreed that this gene was recommended for the WGS panel based on a broader phenotype view to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP. This panel includes conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation. This panel as going to be used for R78, but subsequently during the follow up call on 21st June with the Test Group it was agreed that it was more clinically relevant for R78 to be restricted to genes that are associated with isolated neuropathy and as a result a new panel was created https://panelapp.genomicsengland.co.uk/panels/846/ for this purpose.

Created: 7 Dec 2019, 6:08 p.m. | Last Modified: 7 Dec 2019, 6:08 p.m.

Panel Version: 1.352

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.

Created: 9 May 2019, 5 p.m.

Red List (low evidence)

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Neuropathy a common feature in SCAR1

Created: 8 Jul 2016, 4:09 a.m.

Comment on mode of inheritance: SCA is biallelic

Created: 8 Jul 2016, 4:08 a.m.

Comment on list classification: This gene is in the Charcot Marie Tooth Disease section in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual, for testing of dHMN.

Created: 10 Jun 2016, 1:26 p.m.

Comment on list classification: Multiple variants and cases reported for spinocerebellar ataxia on OMIM.

Created: 5 May 2016, 9:43 a.m.

Green List (high evidence)

Three families originally described (different mutations), identified by linkage and sanger seq of region. Knock in mouse with phenotypes

Created: 9 Dec 2015, 8:50 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Only single family described

Created: 8 Dec 2015, 3:06 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted