Hereditary neuropathy or pain disorder

Gene: TWNK

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 24 Feb 2025, 5:02 p.m. | Last Modified: 24 Feb 2025, 5:02 p.m.

Panel Version: 6.148

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Comment on list classification: TWNK is associated with multiple phenotypes that feature peripheral neuropathy (Mitochondrial DNA depletion syndrome 7 (hepatocerebral type), OMIM:271245 (AR); Perrault syndrome 5, OMIM:616138 (AR); Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3, OMIM:609286 (AD)) - sufficient cases with dominant and recessive forms of disease to support the association.

The scope of this panel has now been expanded to complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.

Created: 6 Nov 2024, 12:57 p.m. | Last Modified: 6 Nov 2024, 12:57 p.m.

Panel Version: 6.116

Red List (low evidence)

Unable to find any evidence of clear neuropathy association

Created: 29 Apr 2019, 12:30 p.m.

Phenotypes
Hereditary Neuropathies

I don't know

Gene rated Amber : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart): Extension of panel scope - minor feature / Broader phenotype: mitochondrial, comment that neuropathy is not common

Created: 7 Dec 2019, 12:03 a.m. | Last Modified: 7 Dec 2019, 12:03 a.m.

Panel Version: 0.86

This gene has changed ratings because the panel for R78 was going to be a broad panel (to include conditions where neuropathy is part of a more complex phenotype or where there is overlap with another neurological presentation eg. HSP) 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, which this panel represents. For genes that represent the broader phenotype see https://panelapp.genomicsengland.co.uk/panels/85/.

Created: 6 Dec 2019, 10:25 p.m. | Last Modified: 6 Dec 2019, 10:25 p.m.

Panel Version: 0.84

Review and rating uploaded from file (Curation_Template_GMS_Neuro_AR_20190521.xlsx) submitted by Alex Rossor (UCL Institute of Neurology) on behalf of London North GLH for GMS Neurology specialist test group.

Created: 11 Jun 2019, 1:40 p.m.

Review and rating submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.

Created: 29 Apr 2019, 12:53 p.m.

added new-gene-name tag, new approved symbol is TWNK

Created: 22 May 2017, 11:36 a.m.

Comment on list classification: Demoted from amber to red due to reviewer's comments and review.

Created: 4 May 2016, 8:35 a.m.

Red List (low evidence)

it causes PEO and mild cardiac involvement and myopathy, to my experience neuropathy is very rare in this gene defect

Created: 9 Dec 2015, 4:47 p.m.

Green List (high evidence)

Multiple reports of variants cuasing peripheral neuropathy and should be included in R78

Created: 20 Oct 2024, 11:02 a.m. | Last Modified: 20 Oct 2024, 11:02 a.m.

Panel Version: 5.19

Complex mitochondrial phenotype

Created: 9 Dec 2015, 8:49 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Deafness, ovarian dysgenesis, learning difficulties, delayed motor development, cerebellar hypoplasia, peripheral axonal neuropathy

Publications

• 37932750: 32281099: 32234020: 24061067: 20880070 :

Complex mitochondrial phenotype

Created: 8 Dec 2015, 3:05 p.m.