Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes Zellweger Spectrum Disorder

Zellweger spectrum disorders (ZSDs) are autosomal-recessive disorders that are caused by defects in peroxisome biogenesis due to bi-allelic mutations in any of 13 different PEX genes. Here, we identified seven unrelated individuals affected with an apparent dominant ZSD in whom a heterozygous mutant PEX6 allele (c.2578C>T [p.Arg860Trp]) was overrepresented due to allelic expression imbalance (AEI). We demonstrated that AEI of PEX6 is a common phenomenon and is correlated with heterozygosity for a frequent variant in the 3 ′ untranslated region (UTR) of the mutant allele, which disrupts the most distal of two polyadenylation sites.

Source: The American Journal of Human Genetics - December 7, 2017 Category: Genetics & Stem Cells Authors: Kim D. Falkenberg, Nancy E. Braverman, Ann B. Moser, Steven J. Steinberg, Femke C.C. Klouwer, Agatha Schl üter, Montserrat Ruiz, Aurora Pujol, Martin Engvall, Karin Naess, FrancJan van Spronsen, Irene Körver-Keularts, M. Estela Rubio-Gozalbo, Sacha Ferd Tags: Article Source Type: research