Genotype-Degree of hemolysis Correlation in Hereditary Spherocytosis

Abstract Objective: To investigate the potential genotype-degree of hemolysis association in hereditary spherocytosis (HS). Methods: 23 HS patients in our cohort all conducted next-generation sequencing (NGS) to detect erythrocyte membrane protein gene mutations and Levitt's carbon monoxide (CO) breath test to detect erythrocyte (RBC) lifespan. The data of RBC lifespan were statistically analyzed according to different mutation genes, types and sites. Results: There were 8 ANK1,9 SPTB,5 SLC4A1 and 1 SPTA1 mutations in our cohort, and the median RBC lifespan of 23 HS patients was 14(8-48) days. The median RBC lifespan of patients with ANK1, SPTB and SLC4A1 mutations was 13(8-23), 13(8-48) and 14(12-39) days, with no statistically significant difference( P =0.618). The median RBC lifespan of patients with missense, splice and nonsense/insertion/deletion mutations was 16.5 (8-48), 14 (11-40) and 13(8,-20) days, respectively, with no statistical difference( P =0.514). The median RBC lifespan of patients with mutations located in the spectrin-binding domain and the non-spectrin-binding domain was 14(8-18) and 12.5(8-48) days, with no statistical difference( P =0.959). 25% of patients with mild hemolysis carried ANK1 or SPTA1 mutations and 75% carried SPTB or SLC4A1 mutations, while 46.7% of patients with severe hemolysis had ANK1 or SPTA1 mutations and 53.3% had SPTB or SLC4A1 mutations. The composition of mutated genes did not differ statistically between the two groups( P =0.400). Conclusion: This is the first study focusing on the genotype-degree of hemolysis association in HS. Our findings indicate that there is no clear correlation between genotype and degree of hemolysis in HS.