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| Childhood onset hereditary spastic paraplegia v1.166 | GCH1 | Louise Daugherty commented on gene: GCH1: Amber gene with Green 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.165 | GCH1 |
Louise Daugherty Source Expert Review Green was added to GCH1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Childhood onset hereditary spastic paraplegia v1.134 | GCH1 | Louise Daugherty Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.75 | GCH1 | Louise Daugherty Source Yorkshire and North East GLH was added to GCH1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.74 | GCH1 | Nick Beauchamp reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.74 | GCH1 | Louise Daugherty commented on gene: GCH1: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.54 | GCH1 |
Louise Daugherty commented on gene: GCH1: Amber rating on Hereditary spastic paraplegia panel 1.198 Comment on list classification: Kept rating as Amber following clinical review from Helen Brittain- Amber rating is appropriate for now, based upon the two cases and some phenotypic queries. Rebecca Foulger (Genomics England curator), 2 Mar 2019 Comment on mode of inheritance: Both literature cases (PMID:24509643; 21935284) are heterozygous, so have kept MOI as Monoallelic for now while gene is rated Amber. Note that OMIM displays AR and AD inheritance for Dystonia, DOPA-responsive, with or without hyperphenylalaninemia (MIM:128230). Rebecca Foulger (Genomics England curator), 28 Jan 2019 Comment on list classification: Updated rating from Grey to Amber awaiting feedback from clinical team. 2 literature cases of HSP phenotype in PMIDs:24509643,21935284 both of which involved previous misdiagnosis of DRD/cerebral palsy. Rebecca Foulger (Genomics England curator), 18 Dec 2018 PMID:21935284 (Lee et al. 2011) report a novel initiation codon mutation (c.1A>T; p.Met1Leu) in GCH1 in a patient with dopa-responsive dystonia (DRD) that had previously been mis-diagnosed as cerbral palsy. Rebecca Foulger (Genomics England curator), 18 Dec 2018 PMID:24509643 (Fan et al 2014) identified a heterozygous GCH1 variant (R216X) by WES in a patient presenting with progressive spastic paraplegia. The R216X variant had been previously reported as causal for dopa-responsive dystonia (MIM:128230), a phenotype that can resemble HSP. Rebecca Foulger (Genomics England curator), 18 Dec 2018 Fan (2014, 24509643) het for nonsense variant previously associated with dopa-responsive dystonia. Authors observe that Dopa-responsive Dystonia can resemble HSP Lee (2011, 21935284), another example of DRD misdiagnosed as Cerebral palsy with GCH1 c.1A>T; p.Met1Leu missense Diagnostic on Sheffield HSP panel Sources: Literature Chris Buxton (North Bristol NHS Trust), 27 Nov 2018. Green rating submitted. |
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| Childhood onset hereditary spastic paraplegia v1.54 | GCH1 | Louise Daugherty Classified gene: GCH1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.54 | GCH1 | Louise Daugherty Gene: gch1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.48 | GCH1 | Louise Daugherty commented on gene: GCH1: 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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.48 | GCH1 | Louise Daugherty reviewed gene: GCH1: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.46 | GCH1 | Louise Daugherty Mode of inheritance for gene: GCH1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.45 | GCH1 | Louise Daugherty Classified gene: GCH1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.45 | GCH1 | Louise Daugherty Gene: gch1 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.7 | GCH1 | Michael Bonello reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.6 | GCH1 | James Polke reviewed gene: GCH1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: Dystonia, Spastic paraplegia, progressive spastic paraplegia, Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.5 | GCH1 | Louise Daugherty Source NHS GMS was added to GCH1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.4 | GCH1 | Louise Daugherty Source London North GLH was added to GCH1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Childhood onset hereditary spastic paraplegia v1.3 | GCH1 |
Louise Daugherty Added phenotypes Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; Dystonia; progressive spastic paraplegia; Spastic paraplegia for gene: GCH1 Publications for gene GCH1 were changed from 21935284; 24509643 to 24509643; 21935284 |
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| Childhood onset hereditary spastic paraplegia v0.6 | GCH1 |
Sarah Leigh gene: GCH1 was added gene: GCH1 was added to Hereditary spastic paraplegia - childhood onset. Sources: Expert Review Amber,Literature Mode of inheritance for gene: GCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GCH1 were set to 21935284; 24509643 Phenotypes for gene: GCH1 were set to progressive spastic paraplegia; Spastic paraplegia; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; Dystonia |
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