Two novel mutations of PEX6 in one Chinese Zellweger spectrum disorder and their clinical characteristics

Background: Zellweger spectrum disorder (ZSD) is an autosomal recessive peroxisome biogenesis disorder (PBD) caused by bi-allelic mutations in any of the 13 PEX family genes. Methods: We reported a Chinese PBD-ZSD patient with compound heterozygous mutations of PEX6 detected by target sequencing and Sanger sequencing. The clinical materials were collected. In silico analysis were used to evaluate the pathogenicity of the two mutations. An updated review summarized the genotype-phenotype correlation of PBD patients with PEX6 mutations. Results: The patient was diagnosed as PBD-ZSD and displayed retinitis pigmentosa, bilateral sensorineural hearing loss, hypotonia, developmental delay, ovarian and enamel dysplasia. Elevated very long chain fatty acids were shown and a pattern of leukodystrophy was displayed through MRI. The two mutations were novel with p.Cys358* and p.Leu83Pro, both classified as pathogenic according to American College of Medical Genetics and Genomics guideline. Phenotype-genotype correlations were shown in the reported patients with PBD-ZSD continuum. Conclusions: we reported the first Chinese PBD-ZSD patient with 2 novel mutations in PEX6. Target sequencing and VLFAC were helpful in diagnosis.