Identification of a new frameshift homozygous variant of PEX3 gene in a preterm infant with profound global developmental delay and bilateral ptosis: a case report and update literature review
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Background Loss-of-function mutations in PEX3 have been associated with Zellweger syndrome (ZS), a severe form of peroxisome biogenesis disorders (PBD, OMIM: 601539) characterized by significant global developmental delay, muscle weakness with bilateral ptosis, cholestasis, hypotonia, and seizures. ZS can be life-threatening if manifested in the neonatal period. Case presentation This study presents a unique case of a male infant with severe ZS whose condition deteriorated despite intensive supportive treatment. Through whole exome sequencing, an intronic variant NM 003630.2:c.288-10T>A, located 10 nucleotides before exon 4 of the PEX3 gene, was identified. Sanger sequencing revealed a homozygous variant in the infant and a heterozygous variant in both parents. Further analysis using reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence confirmed the abnormal transcript of the PEX3 gene caused by a frameshift variant resulting from the PEX3 gene c.288-10T>A mutation. This modification led to a splicing error that deleted exon 4, causing a direct splicing of exons 3 and 5. This alteration produced a truncated protein comprising 32 incorrect amino acids. Conclusions We here report the first case of severe Zellweger spectrum disorders (ZSDs) due to the PEX3 [c.288-10T>A: p.F97Pfs*33] variant in China. This study broadens the known range of severe ZSDs due to PEX3 pathogenic variants.
