A novel missense variant in RBM10 can cause a mild form of TARP syndrome with developmental delay and dysmorphic features

Eri Imagawa, Tsuyoshi Konuma, Emalyn E. Cork, George A. Diaz, Kimihiko Oishi

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish
Pages (from-to)606-612
Number of pages7
JournalClinical Genetics
Volume98
Issue number6
DOIs
StatePublished - Dec 2020

Keywords

  • RBM10
  • RNA binding protein
  • TARP syndrome
  • developmental delay

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