A Chinese newborn with Zellweger syndrome and compound heterozygous mutations novel in the PEX1 gene: a case report and literature review

In this study, we report a male newborn with severe Zellweger spectrum disorder (ZSDs) presenting asphyxia, hypotonia, poor feeding, and dysmorphic facial features. Despite intensive supportive treatment, the boy's condition deteriorated progressively. The patient's diagnosis was made by delayed results after his death. His genetic analysis showed that the boy carried novel compound heterozygous mutation in PEX1 gene (c.2050C > T and c.782_783del). We conducted a literature search and identified 316 patients with ZSD caused by mutations in the PEX1 gene. The p.G843D and p.I700Yfs*42 were the most commonly reported mutations. Among the 316 patients, clinical manifestations were available in 265 patients. The segregation of these patients' manifestation showed that patients with missense PEX1 mutations have a milder phenotype than those with truncating mutations, while the common p.G843D mutations are milder than other missense mutations. Nearly all truncating mutations in PEX1 except for those with premature stop codons near the end of the gene were associated with a severe disease phenotype. These results indicated that all domains of PEX1 were important in the maintenance of normal peroxisome function. The correlation between severity of the disease and type of mutations in PEX1 can be helpful in predicting prognosis among patients with ZSD caused by mutated PEX1.