gene genotype-phenotype correlation in neonates with Zellweger syndrome.

Background: Zellweger syndrome (ZS) is commonly manifested as facial deformities, hypotonia, and liver dysfunction. However, ZS caused by gene mutation shows a broad and dispersed clinical pattern. In this study, the gene in ZS was analyzed to enrich its clinical characteristics. Meanwhile, phenotypic and genotypic characteristics of Zellweger spectrum disorder (ZSD) induced by mutation were evaluated.

Methods: The clinical data of newborn with ZS in our hospital were analyzed retrospectively. We performed WES and found that the infant carried the gene variant. We searched the biomedical literature databases (PubMed, Web of Science, and EMBASE) to compare clinical features and genotypes.

Results: The neonate developed facial deformities, hypotonia, feeding difficulties, and seizures. Her homozygous variant was found in the gene (NM_017929: exon2: c.34del) inherited from both parents. Electronic databases, including our case, reported 32 pathogenic variants in . We found that variation c.292C> T accounted for the largest proportion of mutations (16/66, 24.24%). The proportion of deleterious mutations in ZS patients was significantly higher than that in NALD and IRD patients.

Conclusions: We identified pathogenic variations in the gene and expanded the known mutant spectrum. By comparing patients with mutations, the study determined that a significantly higher percentage of deleterious mutations in ZS was associated with severe clinical phenotypic characteristics.