Hereditary spastic paraplegia - adult onset

Gene: GCH1

Green List (high evidence)

GCH1 (GTP cyclohydrolase 1)
EnsemblGeneIds (GRCh38): ENSG00000131979
EnsemblGeneIds (GRCh37): ENSG00000131979
OMIM: 600225, Gene2Phenotype
GCH1 is in 15 panels

5 reviews

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Green List (high evidence)

Further HSP patients identified using Sheffield panel with monoallelic pathogenic variants.
Created: 9 May 2019, 5:17 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Chris Buxton (North Bristol NHS Trust)

I don't know

Will include in local HSP panel
Created: 27 Apr 2019, 4:17 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Dystonia; Spastic paraplegia; progressive spastic paraplegia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230

Publications

Michael Bonello (The Walton Centre NHS Foundation Trust)

Green List (high evidence)

Upgrade from Amber to Green on the HSP panel. General neurologists may have difficulty distinguishing between patients with HSP and DOPA-responsive dystonia. Therefore if the clinician puts them forward for the HSP panel and this gene isn't included a differential diagnosis could be missed. Importantly - this is a life changing condition that could be treated if a pathogenic variant was identified.
Created: 28 Apr 2019, 4:30 p.m.
Upgrade from Amber to Green on the HSP panel. General neurologists may have difficulty distinguishing between patients with HSP and DOPA-responsive dystonia. Therefore if the clinician puts them forward for the HSP panel and this gene isn't included a differential diagnosis could be missed. Importantly - this is a life changing condition that could be treated if a pathogenic variant was identified.
Created: 26 Apr 2019, 1:33 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230

Louise Daugherty (Genomics England Curator)

I don't know

Green gene with Amber GLH rating, Gene discussed in view of discrepant rating(s) from GLH(s). Green rating agreed at the GMS Neurology Specialist Test Group Webex on 17th May 2019.
Created: 21 May 2019, 4:14 p.m.
Review and rating submitted byJames Polke (Neurogenetics Laboratory,Institute of Neurology, London), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:50 p.m.
Review and rating from Chris Buxton (North Bristol NHS Trust), submitted by Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.
Created: 27 Apr 2019, 4:30 p.m.
Green Review and rating submitted by Michael Bonello (The Walton Centre NHS Foundation Trust), submitted by Diane Cairns on behalf of North West GLH for GMS Neurology specialist test group.
Created: 26 Apr 2019, 1:39 p.m.

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

2 cases of HSP phenotype ipublications- :24509643,21935284. In sheffields HSP panel
Created: 25 Apr 2019, 1:22 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Dystonia; Spastic paraplegia; progressive spastic paraplegia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Yorkshire and North East GLH
  • South West GLH
  • North West GLH
  • Expert Review Green
  • NHS GMS
  • London North GLH
Phenotypes
  • Dystonia
  • progressive spastic paraplegia
  • Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230
  • Spastic paraplegia
OMIM
600225
Clinvar variants
Variants in GCH1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

13 May 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to GCH1.

27 Apr 2019, Gel status: 4

Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Added phenotypes Dystonia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; progressive spastic paraplegia; Spastic paraplegia for gene: GCH1 Publications for gene GCH1 were changed from to 24509643; 21935284

27 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source South West GLH was added to GCH1.

26 Apr 2019, Gel status: 4

Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to GCH1. Mode of inheritance for gene GCH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

25 Apr 2019, Gel status: 3

Added New Source, Set mode of inheritance, Set Phenotypes, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to GCH1. Mode of inheritance for gene GCH1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes Dystonia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; progressive spastic paraplegia; Spastic paraplegia for gene: GCH1 Rating Changed from Red List (low evidence) to Green List (high evidence)

24 Apr 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to GCH1.

24 Apr 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: GCH1 was added gene: GCH1 was added to Hereditary spastic paraplegia - adult onset. Sources: London North GLH Mode of inheritance for gene: GCH1 was set to