What We Know

• Researchers at Mount Sinai in New York discovered that mutations (tiny changes) in a specific non-coding gene—RNU2‑2—can lead to a severe brain development disorder in children. This was unexpected because RNU2‑2 was previously thought to be inactive or just a “pseudogene.” Nature

The Key Gene: RNU2-2

• This gene produces part of a massive molecular machine called the major spliceosome, which helps process most of our gene transcripts (over 99% of those long messages called introns).

• Only two specific mutations—at positions 4 and 35 of RNU2‑2—were repeatedly found in affected children, pointing to their importance.

How Scientists Discovered It

• The Mount Sinai team, under the direction of Dr. Ernest Turro, analyzed data from the UK’s 100,000 Genomes Project, comparing children with unexplained neurodevelopmental issues to others. RNU2‑2 stood out, alongside another gene they had previously studied.

• Initially, nine children carried one of these de novo mutations (new changes not inherited from parents). Then they confirmed the finding with 16 more cases across different datasets—33 children in total.

Symptoms and Impact

Children with these mutations showed:

• Developmental problems like intellectual disability, speech/motor delay, and in some cases autistic behavior

• Particularly high rates of:

  • Epilepsy (seizures) — all cases had strong, early-onset, hard-to-control seizures

  • Microcephaly (smaller head size)

  • Low muscle tone (hypotonia)

  • Severe global developmental delay

  • Hyperventilation (quick, deep breathing) — a symptom especially enriched in this group

Importantly, these signs seem more severe and distinctive compared to disorders involving a similar gene, RNU4‑2.

Why It's Surprising—and Important

• RNU2‑2 was largely seen as a “pseudogene” (inactive), but the team proved it’s active, produces actual RNA, and is vital during development.

• The mutations occur in regions that play a crucial role in splicing—specifically, where the RNA interacts with other parts of the spliceosome machinery.

• However, when researchers looked at blood samples, they didn't see obvious mistakes in the way other genes are being spliced. That suggests the problem might show up only in brain cells or at different developmental stages.