Identification of a de novo ANK1 Variant in a Patient with Hereditary Spherocytosis on Multi-gene Panel Testing
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Hereditary spherocytosis (HS) is caused by defects in red blood cell membrane components encoded by SPTA1, SPTB, ANK1, SLC4A1, and EPB42. The low sensitivity and specificity of conventional tests such as peripheral blood smear and osmotic fragility test (OFT) limit the diagnosis of HS, especially in patients with mild phenotypes and no family history of the condition. Mutations in ANK1, which encodes ankyrin-1 protein, are present in more than half of HS cases and is known as the most common cause of HS in Korea. Mutations in ANK1 are mostly inherited in an autosomal dominant manner. Here, we report the case of a Korean patient with HS carrying a de novo mutation in ANK1. The patient was suspected of having HS due to neonatal jaundice and clinical manifestations of hemolysis, but the OFT results were unclear. At the age of 20, the patient was definitively diagnosed with HS, caused by a de novo heterozygous ANK1 variant c.856C>T (p.Arg286*), using next-generation sequencing-based multi-gene panel testing and Sanger sequencing analysis.
Abstract
Hereditary spherocytosis (HS) is caused by defects in red blood cell membrane components encoded by SPTA1, SPTB, ANK1, SLC4A1, and EPB42. The low sensitivity and specificity of conventional tests such as peripheral blood smear and osmotic fragility test (OFT) limit the diagnosis of HS, especially in patients with mild phenotypes and no family history of the condition. Mutations in ANK1, which encodes ankyrin-1 protein, are present in more than half of HS cases and is known as the most common cause of HS in Korea. Mutations in ANK1 are mostly inherited in an autosomal dominant manner. Here, we report the case of a Korean patient with HS carrying a de novo mutation in ANK1. The patient was suspected of having HS due to neonatal jaundice and clinical manifestations of hemolysis, but the OFT results were unclear. At the age of 20, the patient was definitively diagnosed with HS, caused by a de novo heterozygous ANK1 variant c.856C>T (p.Arg286*), using next-generation sequencing-based multi-gene panel testing and Sanger sequencing analysis.
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