Diagnostic Odyssey in an Adult Patient with Ophthalmologic Abnormalities and Hearing Loss: Contribution of RNA-Seq to the Diagnosis of a PEX1 Deficiency

Munoz-Pujol G, Alforja-Castiella S, Casaroli-Marano R, Morales-Romero B, Garcia-Villoria J, Yepez VA, Gagneur J, Gusic M, Prokisch H, Tort F, Ribes A (2022)

Publication Type: Journal article

Publication year: 2022

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 23

Article Number: 12367

Journal Issue: 20

DOI: 10.3390/ijms232012367

Abstract

Peroxisomal biogenesis disorders (PBDs) are a heterogeneous group of genetic diseases. Multiple peroxisomal pathways are impaired, and very long chain fatty acids (VLCFA) are the first line biomarkers for the diagnosis. The clinical presentation of PBDs may range from severe, lethal multisystemic disorders to milder, late-onset disease. The vast majority of PBDs belong to Zellweger Spectrum Disordes (ZSDs) and represents a continuum of overlapping clinical symptoms, with Zellweger syndrome being the most severe and Heimler syndrome the less severe disease. Mild clinical conditions frequently present normal or slight biochemical alterations, making the diagnosis of these patients challenging. In the present study we used a combined WES and RNA-seq strategy to diagnose a patient presenting with retinal dystrophy as the main clinical symptom. Results showed the patient was compound heterozygous for mutations in PEX1. VLCFA were normal, but retrospective analysis of lysosphosphatidylcholines (LPC) containing C22:0–C26:0 species was altered. This simple test could avoid the diagnostic odyssey of patients with mild phenotype, such as the individual described here, who was diagnosed very late in adult life. We provide functional data in cell line models that may explain the mild phenotype of the patient by demonstrating the hypomorphic nature of a deep intronic variant altering PEX1 mRNA processing.

Involved external institutions

Hospital Clínic de Barcelona ES Spain (ES) Universitat de Barcelona (UB) / University of Barcelona ES Spain (ES) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Munoz-Pujol, G., Alforja-Castiella, S., Casaroli-Marano, R., Morales-Romero, B., Garcia-Villoria, J., Yepez, V.A.,... Ribes, A. (2022). Diagnostic Odyssey in an Adult Patient with Ophthalmologic Abnormalities and Hearing Loss: Contribution of RNA-Seq to the Diagnosis of a PEX1 Deficiency. International Journal of Molecular Sciences, 23(20). https://dx.doi.org/10.3390/ijms232012367

MLA:

Munoz-Pujol, Gerard, et al. "Diagnostic Odyssey in an Adult Patient with Ophthalmologic Abnormalities and Hearing Loss: Contribution of RNA-Seq to the Diagnosis of a PEX1 Deficiency." International Journal of Molecular Sciences 23.20 (2022).

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