Abstract
The peroxisomal biogenesis disorders are autosomal recessive diseases morphologically characterised by lacking peroxisomes, biochemically by generalised deficiency of peroxisomal constituent and clinically manifested by serious health problems. Genes involved in the peroxisomal biogenesis are defined as the PEX genes encoding proteins called the peroxins. These peroxins are required for function in assembly of the peroxisomal membrane or in import of the enzymes into the peroxisomes. In this study we present a full overview of the clinical presentation, biochemical and molecular data of patient with Zellweger syndrome from Slovakia. We investigated biochemical metabolites using gas chromatography/mass spectrometry. The presence of causal ins/del mutations we identified by a Sanger sequencing and RFLP. We reported that the patient was a compound heterozygote for mutations in the gene PEX12: a 2-bp insertion (c.767_768dupAT) and a 2-bp deletion (c.887_888delTC). The first one mentioned is a novel mutation, which has not been reported before. Both mutations create a frameshift of the open reading frame which result a premature STOP codon and generate a complete loss of the C-terminal RING finger domain that is crucial for the correct import of proteins into peroxisomes. We found causal mutations responsible for a severe phenotype, and moreover we noted a novel mutation c.767_768dupAT that has not been reported before. The presence of mutations was studied in all family members, and the resulting data were successfully utilized for prenatal diagnosis.
References
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Acknowledgments
We thank Bzdúch and Brennerová from Children’s University Hospital, Department of Pediatrics, Bratislava for supplying of patient sample and documentations. This study is the result of the implementation of the project „University Scientific Park of the Comenius University in Bratislava“(ITMS 26240220086) supported by the Research and Development Operational Programme funded by the European Regional Development Fund.
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Konkoľová, J., Petrovič, R., Chandoga, J. et al. A novel mutation in the PEX12 gene causing a peroxisomal biogenesis disorder. Mol Biol Rep 42, 1359–1363 (2015). https://doi.org/10.1007/s11033-015-3885-7
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DOI: https://doi.org/10.1007/s11033-015-3885-7