Short summary

In this ongoing study we describe an international cohort of individuals with RBM10 variants, and describe the phenotypes to belong to a broader spectrum than previously known. We find a complex genotype-phenotype correlation. So far, we have shown that the severity of the phenotype is correlated with the amount of functional RBM10 protein. We have also shown that some RBM10 variants resulted in both gain of function and loss of functions in its ability to regulate splicing.

Rationale

Severe loss of function variants in the splicing regulatory protein RBM10 are known to cause the severe X-linked TARP syndrome (TARP is an acronym for Talipes, Atrial septal defect, Robin Sequence, and Persistent left superior vena cava). In its classical form TARP syndrome leads to death in infancy. In recent years, individuals with RBM10-variants associated with milder phenotypes have been published. Our interest in the RBM10 gene started with finding of an RBM10 missense variant in a boy and his maternal uncle with moderate intellectual disability, and with out features of TARP syndrome. The goal with the present study is to confirm that missense variants can indeed be disease causing and to explore the genotype-phenotype correlation. So far, we have proven that the genotype-phenotype correlation is indeed very complex, and that missense variant as well as loss of function variants can cause disease depending on their location and the level of RBM10 function. The study has already resulted in a PhD-thesis, and is an ongoing study. The results from this study so far are in preprint at medRxiv https://doi.org/10.1101/2025.08.05.25330579

Description of the cohort

Individuals with RBM10 variants from all over the world.

Data and biological material

Clinical information and blood samples. Fibroblasts if available.

Collaborating researchers and departments

Institute of Biomedicine and Molecular Biology

• Jeanne Bang Vejen
• Brage Storsten Andresen
• Thomas Koed Doktor

Clinicians from worldwide