Our laboratory has incorporated long-read sequencing into our repeat expansion testing program to complement established PCR and repeat-primed PCR methodologies. Long-read sequencing enables more accurate repeat sizing (especially of large expansions) and direct characterization of repeat sequence composition, providing enhanced resolution of complex repeat regions. This is particularly beneficial for genes such as RFC1 and FGF14, where multiple repeat motifs have been described. While conventional PCR-based methods may detect the presence of an atypical repeat pattern, they may not always be able to identify the specific repeat motif, leading to inconclusive results. By directly sequencing the repeat region, long-read sequencing can provide more comprehensive characterization of these complex expansions, improving diagnostic accuracy and clinical interpretation.
Please note that because this methodology requires high-quality, high-molecular-weight DNA, buccal swab specimens will no longer be accepted for repeat expansion panel testing (i.e. Ataxia Repeat Expansion Panel, Comprehensive Ataxia Testing). Blood and saliva specimens remain acceptable and are well suited for long-read sequencing analysis. If requested by the ordering provider, our laboratory will provide saliva collection kits for patients requiring repeat expansion testing. Buccal swab specimens continue to be accepted for single gene repeat expansion testing.