Draft:RNU4-2 Syndrome

 RNU4-2 Syndrome or Neurodevelopmental disorder with hypotonia, brain anomalies, distinctive facies, and absent language (NEDHAFA) is an inherited disorder caused by mutations in the human gene RNU4-2, which encodes an RNA component of the major spliceosome. It is characterized by hypotonia, global developmental delay, severely impaired intellectual development with poor or absent speech, delayed walking or inability to walk, feeding difficulties with poor overall growth, dysmorphic facial features, and brain anomalies, including ventriculomegaly and progressive white matter loss. 

RNU4-2 Syndrome is one of the most prevalent monogenic neurodevelopmental disorders, with an estimated prevalence second only to Rett syndrome. It is a dominantly inherited genetic disorder caused by mutations in RNU4-2, a gene on chromosome 12, which encodes the small nuclear RNA (snRNA) U4, a component of the small nuclear ribonuculeoprotein (snRNP) U4. snRNP U4 is a component of the major spliceosome, a structure necessary for RNA splicing. Most cases of RNU4-2 Syndrome are explained by a 1-bp insertion (n.64_65insT, NR_003137.2), which is thought to disrupt the interactions of snRNA U4 with the snRNA U6, affecting the stability of the ACAGAGA loop of U6 sRNA which binds 5' splice sites and induces splicing after U4-U6 unwinding.

The genetic etiology of RNU4-2 Syndrome was first identified by the English statistician Daniel Greene working at the Icahn School of Medicine at Mount Sinai through the Bayesian analysis of data collected by Genomics England, with replication in the NIHR BioResource. It was subsequently discovered and published independently by Yuyang Chen of the University of Oxford.