rs1572360944

Description

Here, we report a novel de- novo splice site variant in the Ribosomal Protein S7 (RPS7) gene identified in patient with clinical feature of DBA. We conducted extensive clinical examination including initial hematological examination. To characterize the genetic insult associated with patient's clinical condition, we conducted whole exome sequencing and identified an ultra-rare likely pathogenic de novo splice site variant in RPS7 (NM_001011.4:c.508-3T>G). In silico predications showed the deleterious effect of the splice site variant, which could lead to aberrant splicing. We performed in vitro splicing assays in human cervical cancer (HeLa) cells using RPS7 mini-genes derived from patient's genomic DNA. We detected aberrant splicing event and subsequent reduction in RPS7 gene expression in Hela cells transfected with mutant construct, suggesting non- sense mediated decay (NMD). Furthermore, investigation of RPS7 splicing and transcript expression level in patient's cells validated the results from mini-gene assays. Together, findings from current study indicate that RPS7 splice site mutation (c.508-3 T>G) could lead to aberrant splicing, NMD and subsequent dysfunctioning of ribosomal protein S7, which can lead to clinical symptoms of DBA.