Curating the Clinical Genome 2024 ePoster Gallery-Exploring the Diagnostic Ability of RNA-Seq to Identify Disease-Causing Variants in Muscular Dystrophy

Exploring the Diagnostic Ability of RNA-Seq to Identify Disease-Causing Variants in Muscular Dystrophy

Pdf Summary

The document explores the diagnostic potential of RNA-seq in identifying disease-causing variants in Muscular Dystrophy. Muscular dystrophies are genetic conditions characterized by progressive muscle weakness, often with undiagnosed cases due to variants of unknown significance (VUS) found in DNA sequencing. In this study, RNA-seq analysis of a patient revealed aberrant splicing of the SGCA gene associated with a homozygous VUS. Functional assays were conducted, including minigene assays, western blots, and NMD assays, to provide evidence of pathogenicity. The use of cycloheximide (CHX) aided in validating mutant SGCA transcripts. The document includes experimental plans, results, and references supporting the findings. Undiagnosed individuals with muscle weakness underwent muscle biopsies and RNA sequencing, presenting an alternative diagnostic approach to DNA sequencing. The document also highlights the families of undiagnosed individuals and the medical information, genotype/phenotype, and diagnostic challenges they face. Overall, the study showcases the potential of RNA-seq in identifying disease-causing variants and sheds light on the importance of functional assays in confirming pathogenicity.

Keywords

RNA-seq

Muscular Dystrophy

disease-causing variants

SGCA gene

aberrant splicing

variants of unknown significance

functional assays

cycloheximide

pathogenicity

muscle biopsies