2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Validation of optical genome mapping as a laboratory-developed diagnostic test for facioscapulohumeral muscular dystrophy type 1

Validation of optical genome mapping as a laboratory-developed diagnostic test for facioscapulohumeral muscular dystrophy type 1

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This document describes the validation of an optical genome mapping (OGM) laboratory-developed test for the diagnosis of facioscapulohumeral muscular dystrophy type 1 (FSHD1). FSHD is a common form of muscular dystrophy that is caused by a reduction in the number of D4Z4 repeat elements on chromosome 4q. The OGM approach used in this study was found to have 100% specificity, sensitivity, accuracy, and precision compared to the standard of care. The OGM assay involves isolating ultra-high molecular weight DNA from blood samples and labeling the DNA for imaging. The study included 44 samples, including healthy donor blood samples, cell lines with and without D4Z4 repeat contractions, and individuals suspected of having FSHD1. The results showed concordance in detecting FSHD1-positive samples and accurately identifying the number of repeat units. The OGM assay was found to be highly accurate, repeatable, and reproducible, with a turnaround time of 3-4 days. The study also demonstrated that OGM can eliminate the need for traditional and cumbersome assays such as Southern blotting. Mosaicism, the presence of multiple contracted or non-contracted D4Z4 alleles, was also assessed, and the OGM assay showed a high detection rate for both contracted and non-contracted alleles. The lower limit of detection was established to be 17% for the contracted allele. Overall, the study concludes that the OGM assay is a reliable and efficient method for diagnosing FSHD1 in a clinical setting.

Asset Subtitle

Presenting Author - Alex R. Hastie, PhD; Co-Author - Alka Chaubey, MS, BS, PhD; Co-Author - Karena Kosco, PhD; Co-Author - Arthi Sridhar, PhD;

Meta Tag

Clinical Applications of Molecular Cytogenetics

Genetic Testing

Molecular Cytogenetics

Co-Author Alka Chaubey, MS, BS, PhD

Co-Author Karena Kosco, PhD

Co-Author Arthi Sridhar, PhD

Presenting Author Alex R. Hastie, PhD

Keywords

optical genome mapping

OGM

FSHD1

muscular dystrophy

D4Z4 repeat elements

ultra-high molecular weight DNA

blood samples

sensitivity

specificity

clinical setting