학술논문
Optical Genome Mapping Enables Detection and Accurate Sizing of RFC1 Repeat Expansions
Document Type
article
Author
Stefano Facchini; Natalia Dominik; Arianna Manini; Stephanie Efthymiou; Riccardo Currò; Bianca Rugginini; Elisa Vegezzi; Ilaria Quartesan; Benedetta Perrone; Shahedah Koya Kutty; Valentina Galassi Deforie; Ricardo P. Schnekenberg; Elena Abati; Anna Pichiecchio; Enza Maria Valente; Cristina Tassorelli; Mary M. Reilly; Henry Houlden; Enrico Bugiardini; Andrea Cortese
Source
Biomolecules, Vol 13, Iss 10, p 1546 (2023)
Subject
Language
English
ISSN
2218-273X
71503749
71503749
Abstract
A recessive Short Tandem Repeat expansion in RFC1 has been found to be associated with cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), and to be a frequent cause of late onset ataxia and sensory neuropathy. The usual procedure for sizing these expansions is based on Southern Blotting (SB), a time-consuming and a relatively imprecise technique. In this paper, we compare SB with Optical Genome Mapping (OGM), a method for detecting Structural Variants (SVs) based on the measurement of distances between fluorescently labelled probes, for the diagnosis of RFC1 CANVAS and disease spectrum. The two methods are applied to 17 CANVAS patients’ blood samples and resulting sizes compared, showing a good agreement. Further, long-read sequencing is used for two patients to investigate the agreement of sizes with either SB or OGM. Our study concludes that OGM represents a viable alternative to SB, allowing for a simpler technique, a more precise sizing of the expansion and ability to expand analysis of SV in the entire genome as opposed to SB which is a locus specific method.