The functional data is incredibly helpful when it comes to variant classification. Scores from the saturation genome editing study separate really nicely between our cases and controls in UK Biobank, for example. But as always there are exceptions and variant interpretation can still be tricky!

Importantly, most of the mutations potentially responsible for this condition fall outside of the #ReNU syndrome critical region – they cluster in other parts of the U4 structure which make contacts with other RNAs and proteins, or within U4 itself.

Through international collaborations and with the help of clinicians across the world, we have assembled a cohort of patients with this new condition and describe the disorder here for the first time.

Besides clarifying the critical regions of #RNU4-2 linked to #ReNU syndrome, this study found other regions of the gene which are sensitive to mutations, and raised the possibility of a distinct recessive condition related to the same gene.