De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders.

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with NDD. The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64_65insT). We estimate that variants in this region explain 0.41% of individuals with NDD. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to its contiguous counterpart RNU4-1 and other U4 homologs, supporting RNU4-2's role as the primary U4 transcript in the brain. Overall, this work underscores the importance of non-coding genes in rare disorders. It will provide a diagnosis to thousands of individuals with NDD worldwide and pave the way for the development of effective treatments for these individuals.

Relationship Between Self-Compassion and Compassion for Others: The Mediated Effect of Perceived Social Support and Psychological Resilience.

Studies from individualistic cultural contexts have shown there were no or negative significant correlation between self-compassion and compassion (for others). However, there may be a closer association between them in a collectivism and Buddhism culture. This study randomly selected 441 college students in China and used measures of self-compassion, trait compassion (compassion for others), psychological resilience, and perceiving social support to investigate this relationship. The results showed a moderately positive correlation between self-compassion and compassion. Further chain-mediation analyses revealed that self-compassion not only directly predicted compassion for others but also indirectly influenced it through the mediating effects of perceiving social support and psychological resilience. The results of this study suggest that the quality of compassion may be significantly influenced by culture.