HNRNPU-RNDD is typically the result of a de novo variant. A small number of inherited variants have been reported transmitted from a mosaic parent. Other inherited variants have had their clinical validity questioned (for example, p.Gly218fs*). Nonsense, frameshift, splice site, indels, and damaging missense variants are present across the gene, clustering in exons 1, 9, and 10.
HNRNPU-RNDD is likely caused by haploinsufficiency, although the pathomechanism for missense variants has yet to be explored in depth.
HNRNPU-RNDD may be identified by panel testing, typically for epilepsy or developmental delay/ learning difficulties. This may identify a deletion that is beyond what the panel can report. It is often diagnosed through whole exome or whole genome sequencing. Chromosomal microarray may identify a chromosome 1q44 deletion, which encompass HNRNPU.
A methylation signature has been identified for HNRNPU-RNDD, which may be useful for classifying variants of uncertain clinical significance (VUS).
HNRNPU