Exome sequencing reveals a novel splice site variant in the RPS26 gene in a patient with suspected Diamond-Blackfan anemia

Abstract

Background: Diamond Blackfan anemia (DBA) is an autosomal dominant inherited congenital disease of bone marrow failure, characterized by anemia and malformations. It is mainly associated with mutations in ribosomal protein genes that lead to an imbalance of rRNA biosynthesis. RPS26 was identified to be the disease-causing gene for Diamond-Blackfan anemia. The objectives of the present study were to screen likely pathogenic mutations in a patient with severe red cell aplasia.

Methods: Whole exome sequencing (WES) was performed in combination with Sanger sequencing to identify the causative mutation in a patient with severe red cell aplasia with a clinical phenotype resembling Diamond-Blackfan Anemia.

Results: WES led to the identification of a novel heterozygous splice site mutation, c.182-1G>A in the RPS26 gene, that probably resulted in an aberrant transcript in the patient. The identified splice site mutation was not identified in the proband’s parent as confirmed by Sanger sequencing analysis.

Conclusions: Overall, a novel heterozygous RPS26 splicing variant c.182-1G>A was identified that co-segregated with the DBA phenotypes after comprehensive consideration of the clinical manifestations, genetic analysis, and whole-exome sequencing data.