Inherited white matter disorders

Gene: PEX6

Comment on mode of inheritance: 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.

Created: 1 Apr 2022, 1:55 p.m. | Last Modified: 1 Apr 2022, 1:55 p.m.

Panel Version: 1.156

Comment on mode of pathogenicity: Experimental evidence revealed that rs61753230 has a dominant-negative effect on the function of the PEX1- PEX6 complex in peroxisomal matrix protein import. The unaffected parents analysed were monoallelic for rs61753230 and biallelic for rs144286892, resulting in overexpression of both rs61753230 and wild type alleles (PMID: 29220678).

Created: 1 Apr 2022, 1:54 p.m. | Last Modified: 1 Apr 2022, 1:54 p.m.

Panel Version: 1.154

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, 7:07 a.m.

Comment on phenotypes: Variants also reported in Heimler syndrome 2 616617

Created: 24 Aug 2016, 6:58 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
General Leukodystrophy & Mitochondrial Leukoencephalopathy

Publications

• Parikh et al. Molecular Genetics and Metabolism 114 (2015) 501_642

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