Peroxisomal disorders
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: 15 Jul 2021, 9:36 a.m. | Last Modified: 15 Jul 2021, 9:36 a.m.
Panel Version: 1.13
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Zellweger syndrome
Publications
Variants in this GENE are reported as part of current diagnostic practice
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, 4:22 p.m. | Last Modified: 1 Apr 2022, 4:22 p.m.
Panel Version: 1.18
Comment on mode of inheritance: The mode of inheritance for PEX6 has been 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 for this gene, in order to highlight that unaffected parents may also carry rs61753230.Created: 1 Apr 2022, 4:20 p.m. | Last Modified: 16 Jun 2022, 4:02 p.m.
Panel Version: 1.19
Comment when marking as ready: Associated with phenotype in OMIM and G2P. Numerous variants reported. On the Minimum recommended gene list for broad spectrum genetic testing for single-nucleotide variants associated with leukodystrophies and genetic leukoencephalopathies reported in PMID: 25655951.Created: 24 Aug 2016, 7:05 a.m.
Comment on phenotypes: Variants also reported in Heimler syndrome 2 616617Created: 24 Aug 2016, 7:02 a.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of pathogenicity
Other
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
PEROXISOME BIOGENESIS DISORDER 4B
Publications
Variants in this GENE are reported as part of current diagnostic practice
Penetrance for gene PEX6 was set from to Complete
Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863 to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger) 614862; Peroxisome biogenesis disorder 4B 614863 to Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
Publications for gene: PEX6 were set to
Promoted to V1 3rd October 2016
This gene has been classified as Green List (High Evidence).
Phenotypes for PEX6 were set to Peroxisome biogenesis disorder 4A (Zellweger) 614862; Peroxisome biogenesis disorder 4B 614863
PEX6 was added to Peroxisomal disorderspanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory,UKGTN,Expert list
PEX6 was created by sleigh