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Genet Med. 2019 Mar;21(3):591-600. doi: 10.1038/s41436-018-0103-8. Epub 2018 Jul 12.

microRNAs as biomarkers in Pompe disease.

Author information

1
Department of Translational Medical Sciences, Federico II University, Naples, Italy.
2
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
3
Istituto per le Applicazioni del Calcolo Mauro Picone, Naples, Italy.
4
Department of Neurosciences, University of Messina, Messina, Italy.
5
Department of Biochemistry, Biophysics and General Pathology, Medical Genetics, University of Campania "L. Vanvitelli", Naples, Italy.
6
Department of Neurosciences, University of Torino, Torino, Italy.
7
Department of Neurosciences, Federico II University, Naples, Italy.
8
Ospedale Pediatrico Bambino Ges├╣, Rome, Italy.
9
Azienda Ospedaliera Universitaria Santa Maria della Misericordia, Udine, Italy.
10
Center for Lysosomal and Metabolic Diseases, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
11
Department of Translational Medical Sciences, Federico II University, Naples, Italy. parenti@unina.it.
12
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy. parenti@unina.it.

Abstract

PURPOSE:

We studied microRNAs as potential biomarkers for Pompe disease.

METHODS:

We analyzed microRNA expression by small RNA-seq in tissues from the disease murine model at two different ages (3 and 9 months), and in plasma from Pompe patients.

RESULTS:

In the mouse model we found 211 microRNAs that were differentially expressed in gastrocnemii and 66 in heart, with a different pattern of expression at different ages. In a preliminary analysis in plasma from six patients 55 microRNAs were differentially expressed. Sixteen of these microRNAs were common to those dysregulated in mouse tissues. These microRNAs are known to modulate the expression of genes involved in relevant pathways for Pompe disease pathophysiology (autophagy, muscle regeneration, muscle atrophy). One of these microRNAs, miR-133a, was selected for further quantitative real-time polymerase chain reaction analysis in plasma samples from 52 patients, obtained from seven Italian and Dutch biobanks. miR-133a levels were significantly higher in Pompe disease patients than in controls and correlated with phenotype severity, with higher levels in infantile compared with late-onset patients. In three infantile patients miR-133a decreased after start of enzyme replacement therapy and evidence of clinical improvement.

CONCLUSION:

Circulating microRNAs may represent additional biomarkers of Pompe disease severity and of response to therapy.

KEYWORDS:

Enzyme replacement therapy; Next-generation sequencing; Pompe disease; miR-133a; microRNAs

PMID:
29997386
DOI:
10.1038/s41436-018-0103-8
[Indexed for MEDLINE]

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