%0 Journal Article
%T A novel splice variant in intron 10 of PEX6 is associated with Zellweger Syndrome in a Chinese neonate.
%A Yang P
%A Zhang W
%A Zeng L
%A Tao X
%A Ding K
%A Wang Z
%J Gene
%V 928
%N 0
%D 2024 Nov 30
%M 39013483
%F 3.913
%R 10.1016/j.gene.2024.148767
%X <B>BACKGROUND: </B>Zellweger Syndrome (ZS), or cerebrohepatorenal syndrome, is a rare disorder due to PEX gene mutations affecting peroxisome function. While PEX6 coding mutations are known to cause ZS, the impact of noncoding mutations is less clear.<BR><B>METHODS: </B>A Chinese neonate and his family were subjected to whole exome sequencing (WES) and bioinformatics to assess variant pathogenicity. A minigene assay was also performed for detailed splicing variant analysis.<BR><B>RESULTS: </B>WES identified compound heterozygous PEX6 variants: c.315G>A (p. Trp105Ter) and c.2095-3 T>G. Minigene assays indicated that the latter variant led to abnormal mRNA splicing and the loss of exon 11 in PEX6 expression, potentially causing nonsense-mediated mRNA decay (NMD) or truncated protein structure.<BR><B>CONCLUSIONS: </B>The study suggests that PEX6: c.2095-3 T>G might be a genetic contributor to the patient's condition, broadening the known mutation spectrum of PEX6. These insights lay groundwork for potential gene therapy for such variants.