Adult onset hereditary spastic paraplegia

Gene: PRNP

Green List (high evidence)

PRNP (prion protein)
EnsemblGeneIds (GRCh38): ENSG00000171867
EnsemblGeneIds (GRCh37): ENSG00000171867
OMIM: 176640, Gene2Phenotype
PRNP is in 15 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted' following NHS Genomic Medicine Service approval.
Created: 4 May 2024, 4:56 p.m. | Last Modified: 4 May 2024, 5 p.m.
Panel Version: 4.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Amongst the variable phenotypes seen in carriers of PRNP variants, features of Gerstmann-Straussler disease (OMIM: 137440) have been associated with eight PRNP variants in unrelated cases (p.P105L, p.D178N, p.P102L, p.A117V, p.F198S, p.Q217R, p.G131V, p.H187R (PMIDs: 7902971, 1699173, 1363810, 11709001, 7902972, 19228673).
Created: 8 Jun 2023, 11:22 a.m. | Last Modified: 8 Jun 2023, 11:22 a.m.
Panel Version: 3.10
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Created: 8 Jun 2023, 11:02 a.m. | Last Modified: 8 Jun 2023, 11:02 a.m.
Panel Version: 3.7

Phenotypes
Gerstmann-Straussler disease, OMIM: 137440

James Polke (North Thames GLH)

Green List (high evidence)

HSP can be a rare presenting phenotype for some individuals with inherited prion disease.
Sources: NHS GMS
Created: 31 May 2023, 12:54 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
HSP; Gerstmann–Sträussler–Scheinker disease

Publications

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

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

History Filter Activity

4 May 2024, Gel status: 3

Removed Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_23_promote_green was removed from gene: PRNP.

4 May 2024, Gel status: 3

Added New Source, Status Update

Achchuthan Shanmugasundram (Genomics England Curator)

Source Expert Review Green was added to PRNP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

8 Jun 2023, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183; 1363810

8 Jun 2023, Gel status: 2

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673; 1699173; 7902971; 11709001; 10581485; 10953183

8 Jun 2023, Gel status: 2

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: PRNP were changed from Gerstmann-Straussler disease, OMIM: 137440 to Gerstmann-Straussler disease, OMIM: 137440; Gerstmann-Straussler-Scheinker syndrome, MONDO:0007656

8 Jun 2023, Gel status: 2

Entity classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

Gene: prnp has been classified as Amber List (Moderate Evidence).

8 Jun 2023, Gel status: 0

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350; 16227536; 19228673

8 Jun 2023, Gel status: 0

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q3_23_promote_green tag was added to gene: PRNP.

8 Jun 2023, Gel status: 0

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350

6 Jun 2023, Gel status: 0

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: PRNP were changed from HSP; Gerstmann–Sträussler–Scheinker disease to Gerstmann-Straussler disease, OMIM: 137440

31 May 2023, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance, Set mode of pathogenicity

James Polke (North Thames GLH)

gene: PRNP was added gene: PRNP was added to Adult onset hereditary spastic paraplegia. Sources: NHS GMS Mode of inheritance for gene: PRNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PRNP were set to 30240140; 8250529; 34746379; 28195350 Phenotypes for gene: PRNP were set to HSP; Gerstmann–Sträussler–Scheinker disease Penetrance for gene: PRNP were set to Complete Mode of pathogenicity for gene: PRNP was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: PRNP was set to GREEN gene: PRNP was marked as current diagnostic