Researchers identify a genetic cause of intellectual disability affecting tens of thousands of people

Press release issued: 31 May 2024

A neurodevelopmental disorder, caused by mutations in a single gene, affecting tens of thousands of people worldwide, has been identified by researchers. The work, published today [31 May] in Nature Medicine, was conducted by researchers at the Icahn School of Medicine at Mount Sinai, New York in collaboration with colleagues at the University of Bristol, KU Leuven, Belgium; and the NIHR BioResource (currently based at the University of Cambridge).

Through rigorous genetic analysis, the researchers discovered that mutations in a small non-coding gene called RNU4-2 cause a collection of developmental symptoms that had not previously been tied to a distinct genetic disorder. Non-coding genes are parts of DNA that do not produce proteins. The investigators used whole-genome sequencing data in the UK's National Genomic Research Library to compare the burden of rare genetic variants in 41,132 non-coding genes between 5,529 unrelated cases with intellectual disability and 46,401 unrelated controls.

The discovery is significant, as it represents one of the most common single-gene genetic causes of such disorders, ranking second only to Rett syndrome among patients sequenced by the UK's Genomic Medicine Service. Notably, these mutations are typically spontaneous and not inherited, providing important insights into the nature of the condition.

Read the full University of Bristol news item

Paper: 'Mutations in the U4 snRNA gene RNU4-2 cause one of the most prevalent monogenic neurodevelopmental disorders' by Daniel Greene et al. in Nature Medicine