Mitochondrial disorders
Gene: PPOX
Comment on list classification: There are more than three unrelated cases each with both monoallelic and biallelic variants in PPOX gene. Hence, this gene should be promoted to Green at the next GMS update and the MOI should be updated from 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.Created: 27 Jul 2023, 12:30 p.m. | Last Modified: 27 Jul 2023, 12:30 p.m.
Panel Version: 4.60
As reviewed by Zornitza Stark and suggested in PMID:25778941, Variegate porphyria (VP) should be included in this panel.
Autosomal dominat variegate porphyria (VP):
VP is usually caused by autosomal dominant variants in PPOX gene in the majority of the cases.
PMID:30476629 - Eight unrelated individuals with seven different variants in heterozygous state were reported with VP.
Autosomal dominant variants in this gene have also been associated with VP in OMIM (MIM #176200).
Autosomal recessive variegate porphyria (VP):
PMID:9540991 - A severely affected female proband with recessive VP was identified with two missense compound heterozygous variants in PPOX gene (p.Gly169Glu & p.Gly358Arg), as detected by heteroduplex analysis, automated sequencing, and allele specific oligonucleotide hybridization.
PMID:10870850 - Two unrelated South African cases with variegate porphyria were reported with onset of the disease usually in infancy and with severe skin manifestations. The variant detection included combined SSCP-heteroduplex analysis followed by direct sequencing and both had the common p.Arg59Trp variant, while the other variant was p.Tyr348Cys in one and p.Arg138Pro in the other.
PMID:32247286 - A case of VP was reported from a family with only cutaneous manifestations and was identified with two heterozygous missense variants in PPOX gene (p.Gly41Cys and p.Trp42Arg). The same variants were identified in patient's mother who had skin lesions, whereas father had no clinical involvement and did not have any of these variants. The familly study showed that the two variants occur in cis on the same allele.
PMID:33159949 - A novel homozygous variant in PPOX gene (c.808G>T) was identified in a patient with autosomal recessive form of VP.
Overall, the autosomal recessive form of VP usually occurs early in in fancy and have markedly reduced levels of protoporphyrinogen oxidase than autosomal dominant form. Autosomal recessive VP has not yet been reported in OMIM.
Created: 27 Jul 2023, 10:23 a.m. | Last Modified: 27 Jul 2023, 12:25 p.m.
Panel Version: 4.59
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Porphyria variegata, OMIM:176200
Publications
Variegate porphyria is a disorder of heme metabolism resulting from a deficiency in protoporphyrinogen oxidase, an enzyme located on the inner mitochondrial membrane. A defect in a relevant mitochondrial cofactor, we have included it in our mitochondrial panel in line with the groupings suggested in PMID: 25778941. >3 cases reported.Created: 23 Mar 2020, 12:43 a.m. | Last Modified: 23 Mar 2020, 12:43 a.m.
Panel Version: 2.5
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Porphyria variegata MIM#176200
Publications
Initial gene list and info collated by Carl Fratter (Oxford University Hospitals NHS Trust) January 2019 on behalf of the GMS Mitochondrial specialist test group.Created: 23 Jul 2019, 10:13 a.m. | Last Modified: 23 Jul 2019, 10:13 a.m.
Panel Version: 1.412
Publications for gene: PPOX were set to 9540991; 9811936; 10870850; 12859407; 25778941; 30476629; 32247286; 33159949
Publications for gene: PPOX were set to
Mode of inheritance for gene: PPOX was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Gene: ppox has been classified as Amber List (Moderate Evidence).
Gene: ppox has been classified as Amber List (Moderate Evidence).
Tag Q3_23_MOI was removed from gene: PPOX. Tag Q3_23_promote_green tag was added to gene: PPOX.
Tag Q3_23_MOI tag was added to gene: PPOX.
gene: PPOX was added gene: PPOX was added to Mitochondrial disorders. Sources: NHS GMS,Expert Review Red Mode of inheritance for gene: PPOX was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: PPOX were set to Porphyria variegata, 176200