Activity

Filter

Cancel
Date Panel Item Activity
19 actions
Variegate porphyria v1.3 PPOX Ida Ertmanska Deleted their comment
Variegate porphyria v1.3 PPOX Ida Ertmanska changed review comment from: Comment on mode of inheritance: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with disease onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions along with neurologic and/ or neurodevelopmental symptoms. Hence, the mode of inheritance should be set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' for Variegate porphyria.; to: Comment on mode of inheritance: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with disease onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions along with neurologic and/ or neurodevelopmental symptoms: nystagmus, epileptic seizures, developmental delay, intellectual disability, and sensory neuropathy (PMIDs: 8290408; 9811936; 2004012; 35164799; 37879139; 40114189).
PPOX is associated with AD Variegate porphyria (176200) and AR Variegate porphyria, childhood onset (620483) in OMIM - accessed 13th October 2025.
Hence, the mode of inheritance should be set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' for Variegate porphyria.
Variegate porphyria v1.3 PPOX Ida Ertmanska changed review comment from: Comment on list classification: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions, along with neurologic and/ or neurodevelopmental symptoms: nystagmus, epileptic seizures, developmental delay, intellectual disability, and sensory neuropathy (PMIDs: 8290408; 9811936; 2004012; 35164799; 37879139; 40114189).
PPOX is associated with AD Variegate porphyria (176200) and AR Variegate porphyria, childhood onset (620483) in OMIM - accessed 13th October 2025.
Based on the available evidence, this gene should remain Green for Variegate porphyria.; to: Comment on list classification: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions, along with neurologic and/ or neurodevelopmental
Based on the available evidence, this gene should remain Green for Variegate porphyria.
Variegate porphyria v1.3 PPOX Achchuthan Shanmugasundram Tag Q3_25_MOI tag was added to gene: PPOX.
Variegate porphyria v1.3 PPOX Achchuthan Shanmugasundram Publications for gene: PPOX were set to
Variegate porphyria v1.2 PPOX Achchuthan Shanmugasundram Phenotypes for gene: PPOX were changed from to Variegate porphyria, OMIM:176200; Variegate porphyria, childhood-onset, OMIM:620483; variegate porphyria, MONDO:0008297; variegate porphyria, childhood-onset, MONDO:0957577
Variegate porphyria v1.1 PPOX Ida Ertmanska commented on gene: PPOX: Comment on list classification: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions, along with neurologic and/ or neurodevelopmental symptoms: nystagmus, epileptic seizures, developmental delay, intellectual disability, and sensory neuropathy (PMIDs: 8290408; 9811936; 2004012; 35164799; 37879139; 40114189).
PPOX is associated with AD Variegate porphyria (176200) and AR Variegate porphyria, childhood onset (620483) in OMIM - accessed 13th October 2025.
Based on the available evidence, this gene should remain Green for Variegate porphyria.
Variegate porphyria v1.1 PPOX Ida Ertmanska changed review comment from: Comment on mode of inheritance: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with disease onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions along with neurologic and/ or neurodevelopmental symptoms. Hence, the mode of inheritance should be set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' for Variegate porphyria.; to: Comment on mode of inheritance: Monoallelic PPOX variants usually result in Variegate Porphyria limited to cutaneous manifestations, with disease onset in adolescence or adulthood. Biallelic variants are known to cause Variegate Porphyria with a more severe, early-onset phenotype - skin lesions along with neurologic and/ or neurodevelopmental symptoms. Hence, the mode of inheritance should be set to 'BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal' for Variegate porphyria.
Variegate porphyria v1.1 PPOX Ida Ertmanska edited their review of gene: PPOX: Changed mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Variegate porphyria v1.1 PPOX Ida Ertmanska reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 10486317, 33159949, 35584894, 37879139, 38940544, 40114189; Phenotypes: Variegate porphyria, OMIM:176200, Variegate porphyria, childhood-onset, OMIM:620483, variegate porphyria, MONDO:0008297, variegate porphyria, childhood-onset, MONDO:0957577; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Variegate porphyria v1.1 PPOX Sharon Whatley changed review comment from: Relevant metabolic investigation: urine porphobilinogen (to be completed before genetic testing for diagnosis of an acute porphyria attack), plasma porphyrin fluorescence emission (cutaneous symptoms)
PMID: 35584894 Schulenburg-Brand reports that patients with variegate porphyria (VP) may develop acute attacks often characterised by abdominal pain, nausea, vomiting and other neurological symptoms. They may also present with photosensitive skin lesions. Affected skin is excessively fragile, leading to blisters, milia, and scarring.
PMID: 10486317 Whatley found that skin lesions were the only manifestation of VP in 59% of patients whereas 21% of patients had acute attacks and skin lesions. The remainder having only acute attacks.
PMID: 38940544 Aarsand reports that VP is an autosomal dominant disorder and estimates that individuals with a predisposition for VP in the general population is 1/3,000 (except where founder effects occur e.g. South Africa). A rough estimate of the penetrance of pathogenic variants in this gene is given as 1%. Due to this low penetrance, genetic testing alone may be misleading and cause misdiagnosis. IPNET advises that VP is diagnosed using biochemical tests (when in acute attacks urine porphobilinogen, followed by analysis of plasma fluorescence emission and when cutaneous symptoms alone, plasma porphyrin fluorescence emission s) as the penetrance of variegate porphyria is so low. Genetic testing of the PPOX gene should only be used for family testing so that the genetically predisposed individuals can be advised against precipitating factors such as alcohol and certain drugs.
PMID: 37879139 Assaleh reports that biallelic VP is rare. To the best of our knowledge there are 25 patients (in 21 families) reported with homozygous VP (PMID: 40114189 Kaiser, 37879139 Assaleh, 33159949 Cho and references therein). It usually presents in infancy with severe cutaneous manifestations. In some cases, patients may have hand deformities, nystagmus, growth delay and intellectual disability.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the PPOX gene, due to its low clinical penetrance.; to: Relevant metabolic investigation: urine porphobilinogen (to be completed before genetic testing for diagnosis of an acute porphyria attack), plasma porphyrin fluorescence emission (cutaneous symptoms)
PMID: 35584894 Schulenburg-Brand reports that patients with variegate porphyria (VP) may develop acute attacks often characterised by abdominal pain, nausea, vomiting and other neurological symptoms. They may also present with photosensitive skin lesions. Affected skin is excessively fragile, leading to blisters, milia, and scarring.
PMID: 10486317 Whatley found that skin lesions were the only manifestation of VP in 59% of patients whereas 21% of patients had acute attacks and skin lesions. The remainder having only acute attacks.
PMID: 38940544 Aarsand reports that VP is an autosomal dominant disorder and estimates that individuals with a predisposition for VP in the general population is 1/3,000 (except where founder effects occur e.g. South Africa). A rough estimate of the penetrance of pathogenic variants in this gene is given as 1%. Due to this low penetrance, genetic testing alone may be misleading and cause misdiagnosis. IPNET advises that VP is diagnosed using biochemical tests (urine porphobilinogen during an acute attack followed by plasma porphyrin fluorescence emission or if the patient only has cutaneous symptoms plasma porphyrin fluorescence emission) as the penetrance of variegate porphyria is so low. Genetic testing of the PPOX gene should only be used for family testing so that the genetically predisposed individuals can be advised against precipitating factors such as alcohol and certain drugs.
PMID: 37879139 Assaleh reports that biallelic VP is rare. To the best of our knowledge there are 25 patients (in 21 families) reported with homozygous VP (PMID: 40114189 Kaiser, 37879139 Assaleh, 33159949 Cho and references therein). It usually presents in infancy with severe cutaneous manifestations. In some cases, patients may have hand deformities, nystagmus, growth delay and intellectual disability.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the PPOX gene, due to its low clinical penetrance.
Variegate porphyria v1.1 PPOX Sharon Whatley reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: 35584894, 10486317, 38940544, 37879139; Phenotypes: 176200, 620483; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Variegate porphyria v1.1 Mafalda Gomes Panel version 1.0 has been signed off on 2023-09-14
Variegate porphyria v1.0 Mafalda Gomes promoted panel to version 1.0
Variegate porphyria v0.3 Mafalda Gomes Panel types changed to GMS Rare Disease; GMS signed-off
Variegate porphyria v0.2 Achchuthan Shanmugasundram Panel status changed from internal to public
Variegate porphyria v0.1 PPOX Achchuthan Shanmugasundram reviewed gene: PPOX: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Variegate porphyria v0.1 PPOX Achchuthan Shanmugasundram gene: PPOX was added
gene: PPOX was added to Variegate porphyria. Sources: Expert Review Green,NHS GMS
Mode of inheritance for gene: PPOX was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Variegate porphyria v0.0 Achchuthan Shanmugasundram Added Panel Variegate porphyria
Set list of related panels to R170
Set panel types to: GMS Rare Disease