Hereditary neuropathy or pain disorder
Gene: PPOX
Comment on mode of inheritance: Comment on mode of inheritance: There are at least three cases of variegate porphyria reported with biallelic variants in PPOX gene and sensory neuropathy. Hence, the MOI should be updated from "MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted" to "BOTH monoallelic and biallelic, autosomal or pseudoautosomal" in the next GMS review.Created: 27 Jul 2023, 4:15 p.m. | Last Modified: 27 Jul 2023, 4:15 p.m.
Panel Version: 3.36
PMID:8290408 - The first of the two cases from South Africa (female proband) with "homozygous" variegate porphyria had developed gross sensory neuropathy of the hands and feet.
PMID:10870850 - One of the two South African probands reported with variegate porphyria and biallelic variants (p.Arg59Trp & p.Tyr348Cys) had sensory neuropathy as one of the clinical presentations.
PMID:11286631 - The patient reported with biallelic variants (p.Ile12Thr & p.Pro256Arg) had mild sensory neuropathy.Created: 27 Jul 2023, 4:14 p.m. | Last Modified: 27 Jul 2023, 4:14 p.m.
Panel Version: 3.35
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Porphyria variegata, OMIM:176200; Sensory neuropathy, HP:0000763
Publications
Gene rated Green : From feedback from Genomics England Clinical team (Anna de Burca and Meriel McEntagart). Extension of panel scope - syndrome with non-neurological features / Broader phenotype: variegate porphyria. As per CPOX usually presents more acutely but management implications. Promote to Green as management implicationsCreated: 6 Dec 2019, 8:50 p.m. | Last Modified: 6 Dec 2019, 8:50 p.m.
Panel Version: 0.74
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, 8:49 p.m. | Last Modified: 6 Dec 2019, 8:49 p.m.
Panel Version: 0.74
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.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Skin photosensitivity. Acute episodes similar to AIP.
Publications for gene: PPOX were set to
Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q3_23_MOI tag was added to gene: PPOX.
Gene: ppox has been classified as Green List (High Evidence).
gene: PPOX was added gene: PPOX was added to Hereditary neuropathy NOT PMP22 copy number. Sources: NHS GMS,London North GLH Mode of inheritance for gene: PPOX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: PPOX were set to Porphyria variegata, 176200; Skin photosensitivity. Acute episodes similar to AIP