Retinal disorders

Gene: PEX6

The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 2:08 p.m. | Last Modified: 30 Jan 2023, 2:08 p.m.

Panel Version: 3.26

Retinal involvement is mentioned in Peroxisome biogenesis disorder 4B (OMIM:614863)(PMID:21937992; 22871920).

Created: 1 Apr 2022, 5:07 p.m. | Last Modified: 1 Apr 2022, 5:07 p.m.

Panel Version: 2.250

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, 5:02 p.m. | Last Modified: 1 Apr 2022, 5:02 p.m.

Panel Version: 2.248

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, 4:59 p.m. | Last Modified: 1 Apr 2022, 4:59 p.m.

Panel Version: 2.246

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Mode of pathogenicity
Other

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 10:06 a.m. | Last Modified: 8 Mar 2022, 10:06 a.m.

Panel Version: 2.243

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.

Created: 22 Jan 2021, 1:43 p.m. | Last Modified: 22 Jan 2021, 1:43 p.m.

Panel Version: 2.128

Green List (high evidence)

Heimler syndrome, which represents the mildest end of the peroxisomal biogenesis disorder spectrum, is a rare autosomal recessive disorder characterised by sensorineural hearing loss, enamel hypoplasia of the secondary dentition, nail abnormalities, and retinitis pigmentosa. More than 5 unrelated families reported.
Sources: Expert list

Created: 13 Oct 2020, 7:23 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Heimler syndrome 2, MIM# 616617

Publications

• 27302843
• 32866347
• 31884617
• 29676688
• 26387595

Variants in this GENE are reported as part of current diagnostic practice