학술논문

A TARP Syndrome Phenotype Is Associated with a Novel Splicing Variant in RBM10
Document Type
Report
Source
Genes. November, 2022, Vol. 13 Issue 11
Subject
Germany
Language
English
ISSN
2073-4425
Abstract
TARP syndrome (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistence of the left superior vena cava) is a rare genetic condition, caused by developmental defects during embryogenesis. The phenotypic spectrum of TARP shows high clinical variability with patients either missing cardinal features or having additional clinical traits. Initially, TARP was considered a lethal syndrome, but patients with milder symptoms were recently described. The TARP-locus was mapped to the gene RNA-binding motif protein 10 (RBM10) on the human X-chromosome. We clinically and genetically described a six-year-old boy with a TARP-phenotype. Clinical heterogeneity of symptoms prompted us to sequence the entire exome of this patient. We identified a novel splice variant (NM_005676: c.17+1G>C, p.?) in RBM10. A patient-derived cell line was used to verify the pathogenicity of the RBM10 splice variant by RNA analyses, Western blotting, and immunofluorescence staining. Our molecular genetic findings together with the analyses of progressing clinical symptoms confirmed the diagnosis of TARP. It seems essential to analyze correlations between genotype, phenotype, and molecular/cellular data to better understand RBM10-associated pathomechanisms, assist genetic counseling, and support development of therapeutic approaches.
Author(s): Marta Owczarek-Lipska [1,2,3]; Fenja Markus [1,2]; Eva Bültmann [4]; G. Christoph Korenke [5]; John Neidhardt (corresponding author) [2,3,*] 1. Introduction TARP syndrome (TARP) is caused by mutations in RBM10 [...]