Hereditary neuropathy or pain disorder

Gene: PRNP

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
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Comment on list classification: Neuropathy (predominantly sensory and autonomic) has been reported in at least 7 unrelated families with PRNP-related prion disease, which can present as an early and/or isolated feature. The scope of this panel has now been expanded to include complex forms of neuropathy and therefore this gene can be promoted to Green at the next GMS panel update.

Created: 6 Nov 2024, 3:14 p.m. | Last Modified: 6 Nov 2024, 3:14 p.m.

Panel Version: 6.127

Red List (low evidence)

Gene rated red : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart) Extension of panel scope but limited evidence / Broader phenotype: good evidence for ataxia/oculomotor apraxia, less for more severe phenotype. Alex Rossor felt that there was sufficient evidence that this can cause a neuropathy but that this would be an unusual presentation – suggest that Alex Rossor provide additional evidence for a Green rating on the WGS panel but make Red for the R78 panel

Created: 6 Dec 2019, 2:39 p.m. | Last Modified: 6 Dec 2019, 2:49 p.m.

Panel Version: 0.37

Comment on list classification: 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, 1:22 p.m. | Last Modified: 6 Dec 2019, 2:47 p.m.

Panel Version: 0.37

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)

Just one family

Created: 29 Apr 2019, 9:20 a.m.

Green List (high evidence)

peripheral neuropathy reported as rare presentation of cjd in multiple individuals

Created: 20 Oct 2024, 10:36 a.m. | Last Modified: 20 Oct 2024, 10:36 a.m.

Panel Version: 5.19

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
cjd; dementia; autonomic neuropathy; sensory neuropathy

Publications

• 27716661 : 24224623 : 26768678: 31953922

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Comment on list classification: Gene added by a reviewer, with a second green review.

Created: 9 May 2016, 8:56 a.m.