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

Autor: Gerard Muñoz-Pujol, Socorro Alforja-Castiella, Ricardo Casaroli-Marano, Blai Morales-Romero, Judit García-Villoria, Vicente A. Yépez, Julien Gagneur, Mirjana Gusic, Holger Prokisch, Frederic Tort, Antonia Ribes
Rok vydání: 2022
Předmět:
Trastorns del metabolisme
Hearing Loss
Sensorineural
Hypomorphic Mutation
Macular Oedema
Myopathic Facies
Pex1
Retinal Dystrophy
Rna-seq
Sensorineural Hearing Loss
Very-long Chain Lpc
Inborn errors of metabolism
Deafness
Catalysis
Inorganic Chemistry
Trastorns auditius
Malalties hereditàries
Peroxisomes
Edema
Humans
RNA-Seq
RNA
Messenger
Physical and Theoretical Chemistry
Zellweger Syndrome
Molecular Biology
Spectroscopy
Retrospective Studies
Organic Chemistry
Fatty Acids
Errors congènits del metabolisme
Membrane Proteins
macular oedema
retinal dystrophy
sensorineural hearing loss
myopathic facies
PEX1
hypomorphic mutation
RNA-seq
very-long chain LPC
General Medicine
Hearing disorders
ddc
Computer Science Applications
Ophthalmology
Disorders of metabolism
Oftalmologia
Article
ATPases Associated with Diverse Cellular Activities
Biomarkers
Genetic diseases
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 20; Pages: 12367
Int. J. Mol. Sci. 23:12367 (2022)
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje