A novel missense variant inRBM10can cause a mild form ofTARPsyndrome with developmental delay and dysmorphic features

RBM10, is an RNA binding protein that is important for development by regulating the expression of multiple genes.RBM10is on the X chromosome, and nonsense and frameshiftRBM10variants cause TARP syndrome in males. In a 4-year-old male, we identified a novel maternally inherited missenseRBM10variant in the RRM2 RNA binding domain, c.965C>T, p.Pro322Leu. His clinical features included intellectual disability, developmental delay, growth restriction, hypotonia, and craniofacial malformations. These features were much milder than those described in previously reported cases of TARP syndrome. Byin vitroassays, we found that the mutant p.Pro322Leu RBM10 protein retained its specific RNA binding capacity, while gaining a low-affinity nonspecific RNA binding. It was normally localized to the nucleus, but its expression level was significantly reduced with a significantly short half-life. These results indicated that the p.Pro322Leu missense variant causes a developmental disorder in humans through a unique loss-of-function mechanism.