Arthrogryposis maybe over looked in patients with Peroxisome biogenesis disorder 4A (Zellweger) (OMIM:614862) and Peroxisome biogenesis disorder 4B (OMIM:6148630), as these conditions are characterized by a severe phenotype and premature death in some cases. If this is the case, for Peroxisome biogenesis disorder 4B (OMIM:614863), Falkenberg et al (PMID: 29220678) have 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, 4:46 p.m. | Last Modified: 1 Apr 2022, 4:46 p.m.
Panel Version: 3.157
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, 4:41 p.m. | Last Modified: 1 Apr 2022, 4:41 p.m.
Panel Version: 3.155
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of pathogenicity
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Peroxisome biogenesis disorder 4A (Zellweger) 614862
Penetrance for gene PEX6 was set from to Complete
Tag Q1_22_MOI tag was added to gene: PEX6.
Phenotypes for gene: PEX6 were changed from Peroxisome biogenesis disorder 4A (Zellweger) 614862 to Heimler syndrome 2, OMIM:616617; Peroxisome biogenesis disorder 4A (Zellweger), OMIM:614862; Peroxisome biogenesis disorder 4B, OMIM:614863
Publications for gene: PEX6 were set to 20301621
Mode of inheritance for gene: PEX6 was changed from BIALLELIC, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal
16th Jan 2016: This gene panel was extensively revised with the addition of 101 green genes and review by Alice Gardham. Due to this extensive change to the panel, the decision was made to promote it to the next major version, version 2.
This gene has been classified as Green List (High Evidence).
PEX6 was added to Arthrogryposispanel. Sources: Radboud University Medical Center, Nijmegen,Illumina TruGenome Clinical Sequencing Services,Emory Genetics Laboratory
PEX6 was created by agardham