|
|||||
|
|
A novel missense variant in RBM10 can cause a mild form of TARP syndrome with developmental delay and dysmorphic features |
|
| Authors: | Eri Imagawa Tsuyoshi Konuma Emalyn E. Cork George A. Diaz Kimihiko Oishi |
| Affiliation: | 1. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;2. Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan;3. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA |
| Abstract: | RBM10, is an RNA binding protein that is important for development by regulating the expression of multiple genes. RBM10 is on the X chromosome, and nonsense and frameshift RBM10 variants cause TARP syndrome in males. In a 4-year-old male, we identified a novel maternally inherited missense RBM10 variant 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. By in vitro assays, 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. |
| Keywords: | developmental delay RBM10 RNA binding protein TARP syndrome |