Diagnosis of a mild peroxisomal phenotype with next-generation sequencing

Abstract

Peroxisomal biogenesis disorders (PBD) are caused by mutations in PEX genes, and are typically diagnosed with biochemical testing in plasma followed by confirmatory testing. Here we report the unusual diagnostic path of a child homozygous for PEX1 p.G843D. The patient presented with sensorineural hearing loss, pigmentary retinopathy, and normal intellect. After testing for Usher syndrome was negative, he was found to have PBD through a research sequencing panel. When evaluating a patient with hearing loss and pigmentary retinopathy, mild PBD should be on the differential regardless of cognitive function.

Mild Zellweger syndrome due to functionally confirmed novel PEX1 variants

“…The paper presents diagnostic difficulties in establishing a diagnosis of ZSD in a 21-year-old patient based on Nowadays, next-generation sequencing techniques including gene panels or event whole exome sequencing are new possibilities to identify the molecular background of diseases with an unknown etiology. Because of this, there are an increasing number of patients with a mild phenotype of ZSD initially diagnosed by molecular analysis (Ebberink et al 2010;Ebberink et al 2012;Sevin et al 2011;Ventura et al 2016;Rydzanicz et al 2017). The molecular results, however, should always be interpreted in combination with the clinical phenotype and appropriate laboratory analyses.…”

A metabolomic map of Zellweger spectrum disorders reveals novel disease biomarkers

“…A relatively frequent hypomorphic allele in PEX1 (p.G843D) is observed in the majority of these cases. 4,5 Recently, next-generation sequencing has revealed a wider phenotypic spectrum for many Mendelian disorders. 6 With widespread whole-exome sequencing comes the recognition of additional phenotypes for previously known syndromes, or "phenotypic expansion."…”

Evaluation of C26:0‐lysophosphatidylcholine and C26:0‐carnitine as diagnostic markers for Zellweger spectrum disorders

“…Patients can present with a variety of symptoms and the severity ranges from death in infancy to adults with an isolated vision and hearing deficit (Klouwer et al 2015). With an estimated incidence of 1:50.000 (Gould et al 2001) ZSDs are considered rare, however, an increasing number of patients with a relatively mild phenotype have been identified in recent years (Régal et al 2010;Ebberink et al 2010;Sevin et al 2011;Mignarri et al 2012;Ebberink et al 2012;Ratbi et al 2015;Renaud et al 2016;Ventura et al 2016).…”