Fetal hydrops

Gene: PEX6

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, 3:43 p.m. | Last Modified: 1 Apr 2022, 3:43 p.m.

Panel Version: 1.54

Comment on mode of inheritance: 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 for this gene, in order to highlight that unaffected parents may also carry rs61753230.

Created: 1 Apr 2022, 3:42 p.m. | Last Modified: 8 Sep 2022, 1:50 p.m.

Panel Version: 1.55

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Mode of pathogenicity
Other

Comment on list classification: Updated rating from Red to Green: PMID:20033294 (Dursun et al., 2009) and other reviews (e.g. Table 3 of PMID:23137060) suggest that peroxisomal disorders should be considered in the etiology of hydrops fetalis. PEX6 is on the NGS Non-immune Hydrops Panel for Greenwood Genetic centre: http://www.ggc.org/images/NGS_Hydrops_Panel_Genes_and_Conditions.pdf.

Created: 21 Dec 2016, 2:01 p.m.