Gene. 2024 Jul 14:148767. doi: 10.1016/j.gene.2024.148767. Online ahead of print.
ABSTRACT
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
PMID:39013483 | DOI:10.1016/j.gene.2024.148767
