Serum miRNAs as biomarkers for the rare types of muscular dystrophy

Andrie Koutsoulidou; Demetris Koutalianos; Kristia Georgiou; Andrea C Kakouri; Anastasis Oulas; Marios Tomazou; Tassos C Kyriakides; Andreas Roos; George K Papadimas; Constantinos Papadopoulos; Evangelia Kararizou; George M Spyrou; Eleni Zamba Papanicolaou; Hanns Lochmüller; Leonidas A Phylactou

doi:10.1016/j.nmd.2022.03.003

Serum miRNAs as biomarkers for the rare types of muscular dystrophy

Neuromuscul Disord. 2022 Apr;32(4):332-346. doi: 10.1016/j.nmd.2022.03.003. Epub 2022 Mar 11.

Authors

Andrie Koutsoulidou¹, Demetris Koutalianos², Kristia Georgiou², Andrea C Kakouri³, Anastasis Oulas⁴, Marios Tomazou³, Tassos C Kyriakides⁵, Andreas Roos⁶, George K Papadimas⁷, Constantinos Papadopoulos⁷, Evangelia Kararizou⁷, George M Spyrou⁴, Eleni Zamba Papanicolaou⁸, Hanns Lochmüller⁹, Leonidas A Phylactou¹⁰

Affiliations

¹ Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus; Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus.
² Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus.
³ Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus; Department of Neurogenetics, The Cyprus Institute of Neurology and Genetics, P.O. Box 2346, Nicosia 1683, Cyprus.
⁴ Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus; Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus.
⁵ Yale Center for Analytical Sciences, Yale School of Public Health, 300 George Street, Suite 555, New Haven CT 06520, United States.
⁶ Department of Neuropediatrics, University Hospital Essen, Duisburg-Essen University, Germany; Childrens Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
⁷ Department of Neurology, Eginitio hospital, Medical School of Athens, 74 Vasilissis Sofias, Athens 11528, Greece.
⁸ Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus; Electromyography (EMG) Laboratory, The Cyprus Institute of Neurology and Genetics, P.O. Box 2346, Nicosia 1683, Cyprus.
⁹ Childrens Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada; Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, ON, Canada; Centro Nacional de Análisis Genómico, Center for Genomic Regulation (CNAG-CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Catalonia, Spain.
¹⁰ Department of Molecular Genetics, Function and Therapy, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus; Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, 6 Iroon Avenue, 2371 Ayios Dometios, PO Box 23462, Nicosia 1683, Cyprus. Electronic address: laphylac@cing.ac.cy.

PMID: 35393236
DOI: 10.1016/j.nmd.2022.03.003

Abstract

Muscular dystrophies are a group of disorders that cause progressive muscle weakness. There is an increasing interest for the development of biomarkers for these disorders and specifically for Duchene Muscular Dystrophy. Limited research however, has been performed on the biomarkers' development for the most rare muscular dystrophies, like the Facioscapulohumeral Muscular Dystrophy, Limb-Girdle Muscular Dystrophy and Myotonic Dystrophy type 2. Here, we aimed to identify novel serum-based miRNA biomarkers for these rare muscular dystrophies, through high-throughput next-generation RNA sequencing. We identified many miRNAs that associate with muscular dystrophy patients compared to controls. Based on a series of selection criteria, the two best candidate miRNAs for each of these disorders were chosen and validated in a larger number of patients. Our results showed that miR-223-3p and miR-206 are promising serum-based biomarkers for Facioscapulohumeral Muscular Dystrophy type 1, miR-143-3p and miR-486-3p for Limb-Girdle Muscular Dystrophy type 2A whereas miR-363-3p and miR-25-3p associate with Myotonic Dystrophy type 2. Some of the identified miRNAs were significantly elevated in the serum of the patients compared to controls, whereas some others were lower. In conclusion, we provide new evidence that certain circulating miRNAs may be used as biomarkers for three types of rare muscular dystrophies.

Keywords: Biomarkers; DM2; FSHD1; LGMD2A; Serum; miRNAs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers / blood
Humans
MicroRNAs* / blood
MicroRNAs* / genetics
Muscular Dystrophies, Limb-Girdle* / blood
Muscular Dystrophies, Limb-Girdle* / diagnosis
Muscular Dystrophies, Limb-Girdle* / genetics
Muscular Dystrophy, Facioscapulohumeral* / blood
Muscular Dystrophy, Facioscapulohumeral* / diagnosis
Muscular Dystrophy, Facioscapulohumeral* / genetics
Myotonic Dystrophy* / blood
Myotonic Dystrophy* / diagnosis
Myotonic Dystrophy* / genetics

Substances

Biomarkers
MIRN206 microRNA, human
MIRN363 microRNA, human
MicroRNAs

Grants and funding

FDN-167281/CIHR/Canada