For decades, the study of genetic disease was focused on genes that code for protein. But scientists have now identified a novel neurodevelopmental disorder that is caused by mutations in a gene that does not code for protein, called RNU4-2. These mutations lead to neurological symptoms that cause cognitive dysfunction, but have not previously been linked together as one disease. These findings have been reported in Nature Medicine.
In this work, the investigators analyzed whole-genome sequencing data from over 5,000 cases of intellectual disability and over 46,000 unaffected individuals. The research focused on unusual variations in the sequences of 41,132 genes that do not code for protein. The research revealed a gene that is apparently a common cause of neurodevleopmental problems. The scientists also determined that these mutations often arise spontaneously, and are not usually inherited from a parent.
“Nowadays, finding a single gene that harbors genetic variants responsible for tens of thousands of patients with a rare disease is exceptionally unusual. Our discovery eluded researchers for years due to various sequencing and analytical challenges,” noted first study author Daniel Greene, PhD, an Assistant Professor at the Icahn School of Medicine at Mount Sinai and a Visitor at the University of Cambridge.
This gene surely eluded researchers for so long because it does not code for protein; almost all known genetic neurodevelopmental disorders are caused by mutations in protein-coding genes.
The affected gene is really short at only 141 bases long, but it has a critical role in cellular function, and is crucial to gene splicing, noted senior study author Ernest Turro, PhD, an Associate Professor at Icahn Mount Sinai and a Visitor at the University of Cambridge.
This work will now provide some answers for "tens of thousands of families" by “bringing many diagnostic odysseys to a close.”
The scientists are planning additional studies to learn more about how mutations in this non-coding gene lead to neruodevelopmental issues. Learning more about the disorder is the best way to find treatments and interventions.
Sources: The Mount Sinai Hospital / Mount Sinai School of Medicine, Nature Medicine