The clinical significance of poisoned splicing variants in early-onset neurodevelopmental disorders

Neurodevelopmental disorders (NDDs), which often result from rare highly penetrant genetic variants, present substantial medical, emotional, and financial hardships for affected children and their families. However, despite considerable progress in genomic research and technology, rates of discovery of causal variation among NDD probands remain less than 50%. One possible explanation for this observation is that there exist functional elements within human genomes that harbor causal variation but are missed as a result of incomplete genomic annotation.