Abstract
Zellweger syndrome (ZS) is a consequence of a peroxisome biogenesis disorder (PBD) caused by the presence of a pathogenic mutation in one of the 13 genes from the PEX family. ZS is a severe multisystem condition characterized by neonatal appearance of symptoms and a shorter life. Here, we report a case of ZS with a mild phenotype, due to a novel PEX6 gene mutation. The patient presented subtle craniofacial dysmorphic features and slightly slower psychomotor development. At the age of 2 years, he was diagnosed with adrenal insufficiency, hypoacusis, and general deterioration. Magnetic resonance imaging showed a symmetrical hyperintense signal in the frontal and parietal white matter. Biochemical tests showed elevated liver transaminases, elevated serum very long chain fatty acids, and phytanic acid. After the death of the child at the age of 6 years, molecular diagnostics were continued in order to provide genetic counseling for his parents. Next generation sequencing (NGS) analysis with the TruSight One™ Sequencing Panel revealed a novel homozygous PEX6 p.Ala94Pro mutation. In silico prediction of variant severity suggested its possible benign effect. To conclude, in the milder phenotypes, adrenal insufficiency, hypoacusis, and leukodystrophy together seem to be pathognomonic for ZS.
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The study was supported by the National Science Centre (NCN) Poland, grant number 2013/11/B/NZ7/04944.
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MR and PG performed NGS analysis, TJS performed fatty acid profiling, EJ performed radiological evaluation, EJ performed clinical data collection, GK performed Sanger sequencing for replication study, RP and AT-S conceived and supervised the study, RP, AT-S, and MR drafted the manuscript. All authors read and approved the final manuscript.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Bioethical Committee at the Children’s Memorial Health Institute of Warsaw and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent for the genetic analysis was obtained from all individual participants included in the study. Written consent was obtained for publication of the patient’s photography.
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Communicated by: Michal Witt
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Rydzanicz, M., Stradomska, T.J., Jurkiewicz, E. et al. Mild Zellweger syndrome due to a novel PEX6 mutation: correlation between clinical phenotype and in silico prediction of variant pathogenicity. J Appl Genetics 58, 475–480 (2017). https://doi.org/10.1007/s13353-017-0414-5
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DOI: https://doi.org/10.1007/s13353-017-0414-5