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Muñoz-Pujol, G.* ; Alforja-Castiella, S.* ; Casaroli-Marano, R.* ; Morales-Romero, B.* ; García-Villoria, J.* ; Yépez, V.A.* ; Gagneur, J.* ; Gusic, M. ; Prokisch, H. ; Tort, F.* ; Ribes, A.*

Diagnostic odyssey in an adult patient with ophthalmologic abnormalities and hearing loss: Contribution of RNA-seq to the diagnosis of a PEX1 deficiency.

Int. J. Mol. Sci. 23:12367 (2022)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Hypomorphic Mutation ; Macular Oedema ; Myopathic Facies ; Pex1 ; Retinal Dystrophy ; Rna-seq ; Sensorineural Hearing Loss ; Very-long Chain Lpc
ISSN (print) / ISBN 1422-0067
e-ISSN 1661-6596
Zeitschrift International Journal of Molecular Sciences
Quellenangaben Band: 23, Heft: 20, Seiten: , Artikelnummer: 12367 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Förderungen German Bundesministerium fur Bildung und Forschung (BMBF)
Generalitat de Catalunya

Centre for Biomedical Network Research on Rare Diseases
Instituto de Salud Carlos III