RNU4ATAC-opathy: Clinical, molecular and transcriptomic insights from a large cohort

Genotypic and phenotypic spectrum of RNU4ATAC-opathy, VUS reclassification by RNA-seq through minor intron retention

Sixty individuals with confirmed RNU4ATAC-opathy were recruited from international centers, including 42 previously undescribed cases and 33 distinct RNU4ATAC variants, 13 novel. RNA-seq enabled VUS reclassification as likely pathogenic in 6/7 studied patients, through a consistent minor intron retention pattern. The study highlights significant phenotypic variability, including presentations lacking cardinal features, and underscores that RNU4ATAC variants are frequently overlooked in clinical exome analysis pipelines due to their noncoding nature.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This article complements Cuinat et al. published in the same Genetics in Medicine issue. Together, they redefine RNU4ATAC-opathies as broader and more frequent than previously assumed. Using RNA-seq to reclassify noncoding VUS is an important methodological message for diagnostic laboratories.