Novel ANK1 mutation in hereditary spherocytosis in a northeastern Thai patient: A case report

Hereditary spherocytosis (HS) is the most common hereditary red blood cell membrane defect, characterized by hemolytic anemia, jaundice, and splenomegaly. While HS is well-documented in North America, Europe, and Japan, it is less common in Southeast Asia. This study reports a novel heterozygous ANK1 gene mutation (c.1638 C>A, p.Tyr546*) in a 5-year-old boy from northeastern Thailand, presenting with chronic anemia, hepatosplenomegaly, and gallstones. The mutation leads to a truncated ankyrin-1 protein, contributing to vertical linkage instability of the red cell membrane and resulting in moderate to moderately severe HS. The patient's condition improved following splenectomy, with the cessation of regular transfusion requirements and the development of polycythemia. Genetic analysis through whole-genome sequencing (WGS) did not identify additional pathogenic mutations. The correlation between genotype and disease severity suggests that this specific ANK1 mutation contributes to the moderate to moderately severe disease phenotype. Further studies are needed to explore genotype-phenotype correlations in Thai HS patients. • The study reports a novel unpublished c.1638 C>A, p.Tyr546* in the ANK1 gene, marking the first case in a Thai patient. • Genotype-Phenotype Correlation: The p.Tyr546* in the ANK1 gene is associated with moderate-to-moderately severe hereditary spherocytosis (HS). • Mutation in the N-terminal repeat domain is associated with pincered cells in peripheral blood smear. • The study adds valuable genomics data on HS in Southeast Asia, where such reports are rare, particularly from Thailand.