Nonsense Variant in the β-Spectrin Gene Causing Hereditary Spherocytosis Identified by Whole-Exome Sequencing in a...

Hereditary spherocytosis (HS) is an inherited disease characterized by the presence of spherical erythrocytes in the peripheral blood. Beta-spectrin (SPTB) encodes a cytoskeletal protein previously associated with spherocytosis. Mutations in SPTB are one of the most common causes of HS. We have reported here the case of a 2-year-old boy who presented with severe anemia, jaundice, and hyperbilirubinemia at Kunming Children's Hospital. His osmotic fragility tests (OFT) and eosin maleimide (EMA) tests were positive. Genetic molecular analysis was performed to identify the underlying cause of the disease in the patient and his parents via whole-exome sequencing (WES), and revealed a heterozygous nonsense variant (c.1920G > A: p.W640*) in exon 14 of SPTB. This mutation induced a change from tryptophan to a stop codon at position 640. Sanger sequencing further confirmed that the variant was inherited from the patient's mother. The patient was diagnosed with HS based on the combined analyses of the clinical phenotype and genotype. The cumulative findings enrich the spectrum of SPTB variants, provide valuable clinical molecular insights, and lay the foundation for genetic counseling and diagnosis.