In April of this year, sequencing data from Genomics England revealed that changes in a non-coding RNA gene called RNU4-2 are the cause of the disease in around 0.5% of all patients with syndromic neuronal developmental disorders. These pathogenic changes are usually presented de novo (Chen et al.).
Since RNU4-2 does not encode a protein, it is not enriched in conventional exome kits and is therefore not detected. As one of the first laboratories, CeGaT has responded to this gap and included RNU4-2 into the exome enrichment (CeGaT ExomeXtra®). Pathogenic RNU4-2 changes in the indication “neuronal developmental disorders” and the associated symptoms are thus recognized and reported. Thanks to this measure, we were able to solve the first case by a pathogenic variant in RNU4-2 back in May.
Reference
Chen, Yuyang et al. “De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders.” medRxiv : the preprint server for health sciences 2024.04.07.24305438. 9 Apr. 2024, doi:10.1101/2024.04.07.24305438. Preprint.