A novel EPB41 p.Trp704 mutation in a Korean patient with hereditary elliptocytosis: a case report

Hereditary elliptocytosis (HE) is inherited in an autosomal dominant fashion, and the majority of HE-associated defects occur due to qualitative and quantitative defects in the RBC membrane skeleton proteins α-spectrin, β-spectrin, or protein 4.1R. The complex gene encodes a diverse family of protein 4.1R isoforms which are key components of the erythroid membrane skeleton that regulates red cell morphology and mechanical stability. The purpose of this study was to investigate the genome of a Korean patient with HE to discover the causative gene mutation using gene panel sequencing. An 89-year-old female presented to the Emergency Department and was diagnosed with pancreatitis and gallstones. A peripheral blood smear revealed that approximately 60% of the RBCs were abnormally shaped and appeared oval or elongated, from slightly egg-shaped to rod or pencil forms (elliptocytes). Targeted gene panel sequencing consisting of 33 genes related to inherited RBC disorders and Sanger sequencing were performed. A heterozygous c.2112G > A of the gene leading to premature termination codon (NM_001166005.1:c.2112G > A, p.Trp704*) was identified. This variant, which had not been previously reported to be related to HE, was confirmed by Sanger sequencing. Thus, the patient's diagnosis of HE-1 was genetically confirmed. The present study confirmed a novel mutation of the gene that plays an important role in expanding the mutational distribution in HE-1. It could also be helpful for understanding the correlation between the genotype and phenotype in HE.