Key result
Targeted gene panel sequencing identifies a novel EPB41 mutation in a patient with hereditary elliptocytosis.
Why the study?
The study aimed to investigate the genome of a Korean patient with hereditary elliptocytosis to discover the causative gene mutation using gene panel sequencing.
Case Report (n=1)
Identified a novel EPB41 p.Trp704 mutation causing hereditary elliptocytosis, expanding the known mutational spectrum of the disease.
May inform targeted EPB41 sequencing in unexplained hereditary elliptocytosis; leaves open prevalence, penetrance, and management implications.
Objectives: 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 EPB41 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.Methods: 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.Results: A heterozygous c.2112G > A of the EPB41 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.Conclusion: The present study confirmed a novel mutation of the EPB41 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.
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Shin et al. (2020) conducted a case report in Hereditary elliptocytosis (n=1). Targeted gene panel sequencing was evaluated on Identification of causative gene mutation. Targeted gene panel sequencing identified a novel heterozygous c.2112G > A mutation in the EPB41 gene (p.Trp704) in an 89-year-old Korean female with hereditary elliptocytosis.
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