Repeat expansion disorders impact roughly one in 3,000 individuals and present a wide array of clinical manifestations characterized by the expansion of DNA tandem repeat sequences. Over 50 such disorders have been identified to date, and precise genetic typing is essential for their molecular diagnosis, as the length of the repeats often determines the disease's severity and onset timing. Currently, detection is mainly conducted using PCR-based tests or Southern blotting for significant expansions, but these methods come with several drawbacks including being time-consuming, requiring meticulous optimization, and lacking the capacity to analyze multiple repeat loci simultaneously.

Next-generation sequencing (NGS), with either exome or genome sequencing, is now a standard test for many individuals with a suspected genetic disorder. However, NGS data analysis pipelines focus primarily on detecting SNVs, Indels, and CNVs. Detecting disease-causing repeat expansions from NGS data has become feasible due to recent advances in bioinformatics. Incorporating bioinformatics tools to screen for repeat expansions may permit the diagnosis of repeat expansion disorders during routine diagnostic exome or genome sequencing, allowing accurate genetic counseling of affected individuals and their families and improving clinical outcomes. Although technically feasible, at its current stage, NGS-based repeat expansion detection is difficult because of the complex nature of the repeat loci and accurate detection using various NGS methodologies. Although NGS-based repeat expansion detection is still not readily available as a clinically validated test, such analysis is likely to become routine soon due to the increasing use of exome and genome sequencing and the rapid advancement of computational tools and novel methodologies.

The proposed session aims to update clinicians and laboratory professionals on the latest advances in diagnosing and detecting repeat expansions through cutting-edge sequencing technologies. It will delve into the newly developed databases for repeat expansions and discuss their role in analyzing complex repeat alleles. The session will further explore case studies using sequencing technologies to illustrate the practical considerations, potential, and limits of these tests and the criteria for subsequent follow-up examinations.