Likely inborn error of metabolism - targeted testing not possible
Gene: PEX6The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.Created: 1 Feb 2023, 10:24 a.m. | Last Modified: 1 Feb 2023, 10:24 a.m.
Panel Version: 3.6
For Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) has identified Allelic Expression Imbalance (AEI) as a mechanism responsible for the condition. Affected patients (7 unrelated cases) were monoallelic for rs61753230 (c.2578C>T, p.Arg860Trp) and rs144286892 (c.∗442_445 delTAAA), with these variants being on the same chromosome (cis). It would appear that rs144286892 causes the over expression of the allele that it is on, resulting in over expression of rs61753230. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678). Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import (PMID: 29220678).Created: 1 Apr 2022, 3:58 p.m. | Last Modified: 1 Apr 2022, 3:58 p.m.
Panel Version: 2.238
Comment on mode of inheritance: The Q1_22_MOI tag has been added to this gene. The mode of inheritance for PEX6 should be set to: BOTH monoallelic and biallelic, autosomal or pseudoautosomal, in order to detect the dominant Peroxisome biogenesis disorder 4B (OMIM:614863). Incomplete penetrance has been noted, in order to highlight that unaffected parents may also carry rs61753230.Created: 1 Apr 2022, 3:57 p.m. | Last Modified: 1 Apr 2022, 3:57 p.m.
Panel Version: 2.238
Based on comments from Julia Baptista (Royal Devon and Exeter NHS Foundation Trust) on https://panelapp.genomicsengland.co.uk/panels/114/gene/PEX6/
Heterozygous PEX6 variant(c.2578C>T [p.Arg860Trp]) is pathogenic when in cis with 3'UTR c.∗442_445delTAAA due to allelic expression imbalance.Created: 20 Jul 2021, 12:27 p.m. | Last Modified: 20 Jul 2021, 12:27 p.m.
Panel Version: 2.152
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Peroxisome biogenesis disorder 4A (Zellweger) OMIM:614862; peroxisome biogenesis disorder 4A (Zellweger) MONDO:0013930; Peroxisome biogenesis disorder 4B OMIM:614863; peroxisome biogenesis disorder 4B MONDO:0013931
Publications
Tag Q1_22_MOI was removed from gene: PEX6.
Mode of inheritance for gene PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of pathogenicity for gene PEX6 was changed from to Other Penetrance for gene PEX6 was set from to None
Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
Tag Q1_22_MOI tag was added to gene: PEX6.
Tag Q3_21_MOI was removed from gene: PEX6.
Tag Q3_21_MOI tag was added to gene: PEX6.
Publications for gene: PEX6 were set to 27604308; 29220678; 20301621
Phenotypes for gene: PEX6 were changed from Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4B 614863; Peroxisome biogenesis disorder 4A (Zellweger) 614862 to Peroxisome biogenesis disorder 4A (Zellweger) OMIM:614862; peroxisome biogenesis disorder 4A (Zellweger) MONDO:0013930; Peroxisome biogenesis disorder 4B OMIM:614863; peroxisome biogenesis disorder 4B MONDO:0013931
Publications for gene: PEX6 were set to 27604308
Source NHS GMS was added to PEX6. Source London North GLH was added to PEX6.
Ellen McDonagh: Comment on mode of pathogenici
gene: PEX6 was added gene: PEX6 was added to Inborn errors of metabolism. Sources: Expert Review Green Mode of inheritance for gene: PEX6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PEX6 were set to 27604308 Phenotypes for gene: PEX6 were set to Disorders of peroxisome biogenesis; Peroxisome biogenesis disorder 4B 614863; Peroxisome biogenesis disorder 4A (Zellweger) 614862