Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy: Advancement and Challenges

Stephanie Efthymiou; Richard J. L. F. Lemmers; Venugopalan Y. Vishnu; Natalia Dominik; Benedetta Perrone; Stefano Facchini; Elisa Vegezzi; Sabrina Ravaglia; Lindsay Wilson; Patrick J. van der Vliet; Rinkle Mishra; Alisha Reyaz; Tanveer Ahmad; Rohit Bhatia; James M. Polke; Mv Padma Srivastava; Andrea Cortese; Henry Houlden; Silvère M. van der Maarel; Michael G. Hanna; Enrico Bugiardini

doi:10.3390/biom13111567

Biomolecules (Oct 2023)

Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy: Advancement and Challenges

Stephanie Efthymiou,
Richard J. L. F. Lemmers,
Venugopalan Y. Vishnu,
Natalia Dominik,
Benedetta Perrone,
Stefano Facchini,
Elisa Vegezzi,
Sabrina Ravaglia,
Lindsay Wilson,
Patrick J. van der Vliet,
Rinkle Mishra,
Alisha Reyaz,
Tanveer Ahmad,
Rohit Bhatia,
James M. Polke,
Mv Padma Srivastava,
Andrea Cortese,
Henry Houlden,
Silvère M. van der Maarel,
Michael G. Hanna,
Enrico Bugiardini

Affiliations

Stephanie Efthymiou: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Richard J. L. F. Lemmers: Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Venugopalan Y. Vishnu: Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India
Natalia Dominik: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Benedetta Perrone: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Stefano Facchini: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Elisa Vegezzi: IRCCS Mondino Foundation, 27100 Pavia, Italy
Sabrina Ravaglia: IRCCS Mondino Foundation, 27100 Pavia, Italy
Lindsay Wilson: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Patrick J. van der Vliet: Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Rinkle Mishra: Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India
Alisha Reyaz: Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India
Tanveer Ahmad: Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India
Rohit Bhatia: Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India
James M. Polke: Neurogenetics Laboratory, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK
Mv Padma Srivastava: Department of Neurology, All India Institute of Medical Sciences, New Delhi 110029, India
Andrea Cortese: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Henry Houlden: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Silvère M. van der Maarel: Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Michael G. Hanna: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK
Enrico Bugiardini: Department of Neuromuscular Disorders, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK

DOI: https://doi.org/10.3390/biom13111567
Journal volume & issue: Vol. 13, no. 11
p. 1567

Abstract

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Facioscapulohumeral muscular dystrophy (FSHD) is the second most common muscular dystrophy in adults, and it is associated with local D4Z4 chromatin relaxation, mostly via the contraction of the D4Z4 macrosatellite repeat array on chromosome 4q35. In this study, we aimed to investigate the use of Optical Genome Mapping (OGM) as a diagnostic tool for testing FSHD cases from the UK and India and to compare OGM performance with that of traditional techniques such as linear gel (LGE) and Pulsed-field gel electrophoresis (PFGE) Southern blotting (SB). A total of 6 confirmed and 19 suspected FSHD samples were processed with LGE and PFGE, respectively. The same samples were run using a Saphyr Genome-Imaging Instrument (1-color), and the data were analysed using custom EnFocus FSHD analysis. OGM was able to confirm the diagnosis of FSHD1 in all FSHD1 cases positive for SB (n = 17), and D4Z4 sizing highly correlated with PFGE-SB (p n = 2) and with a duplication of the D4Z4 repeat array. OGM is a promising new technology able to unravel structural variants in the genome and seems to be a valid tool for diagnosing FSHD1.

Published in Biomolecules

ISSN: 2218-273X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: https://www.mdpi.com/journal/biomolecules

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