Authors: Deepak Panwar , Atul Thatai

Abstract

Background: Diamond–Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome characterized by pure red cell aplasia and is commonly caused by variants in ribosomal protein genes. Variants in RPS26 are relatively uncommon, and splice-site changes in this gene are still underreported.

Case Presentation: We describe a 17-month-old female who presented with severe anemia with clinical features suggestive of Diamond–Blackfan anemia. Whole Exome sequencing (WES) identified a novel heterozygous de novo canonical splice-site variant, NM_001029.5:c.182-1G>A in the RPS26 gene. The variant was absent from population databases, including gnomAD, and was also confirmed by Sanger sequencing. In silico analysis using SpliceAI predicted disruption of the canonical splice acceptor site along with activation of a cryptic splice site, suggesting a deleterious effect on normal splicing. However, RNA studies are needed to confirm the exact splicing outcome and to better understand how this variant affects RPS26 function. Based on ACMG/AMP guidelines, the variant was classified as likely pathogenic.

Conclusion: This case contributes to the known mutational spectrum of RPS26 and highlights the value of exome sequencing in the molecular evaluation of patients with suspected DBA.

Keywords: Diamond-Blackfan anemia, RPS26, splice-site variant, Whole Exome sequencing.