Mild Zellweger Syndrome Due to a Novel PEX6 Mutation: Correlation Between Clinical Phenotype and in Silico Prediction of Variant Pathogenicity

Overview

Journal J Appl Genet

Publisher Springer

Specialty Genetics

Date 2017 Oct 20

PMID 29047053

Citations 8

Authors

Malgorzata Rydzanicz

Teresa Joanna Stradomska

Elzbieta Jurkiewicz

Ewa Jamroz

Piotr Gasperowicz

Grazyna Kostrzewa

Rafal Ploski

Anna Tylki-Szymanska

Affiliations

Soon will be listed here.

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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