Identification of Novel Mutations in Children with Hereditary Spherocytosis by Targeted Exome Sequencing: A Single Center Experience

Abstract

Aim: Hereditary spherocytosis (HS) is a prevalent cause of congenital hemolytic anemia in Northern
 Europeans. It is characterized by spherocytes resulting from defects in the erythrocyte structural
 membrane proteins spectrin and ankyrin. To date, more than five candidate genes, including ANK1,
 SPTB, SPTA1, SLC4A1, and EPB42 have been linked to HS. Here, we aim to investigate the presence
 of novel as well as known mutations in eight Turkish children with clinically suspected HS.
 Material and Methods: We presented the clinical features of the patients and identified the causative
 gene variants using targeted exome sequencing. Eight children who were clinically suspected of having
 HS enrolled in this study. A family and medical history, clinical examination, relevant laboratory test
 results, osmotic fragility test (OFT), and genetic results were evaluated.
 Results: Six causative variants, including three ANK1 variants, two SPTB variants and one SLC4A1
 variant were detected. All these mutations were novel variants. ANK1 and SPTB are the most common
 mutant genes in children with HS.
 Conclusion: This study expanded the mutation spectrum of ANK1, SPTB and SLC4A1. This is the first
 study to determine the genetic and clinical characteristics of children with HS in Turkey.