Expanding the genetic spectrum of hereditary spherocytosis: novel mutations and phenotypic heterogeneity from a 55-patient cohort

To characterize the clinical and genetic profiles of patients with hereditary spherocytosis (HS) and report novel mutations. This retrospective study included 55 patients (25 males, 30 females; median age 9 years) with HS admitted between 2016 and 2023. Clinical and laboratory data were analyzed. Targeted next-generation sequencing was performed to detect pathogenic mutations. Comparisons were made using Student's t-test or Mann-Whitney U test. Anemia was present in 53 patients, including 31 with moderate-to-severe anemia; 40 exhibited splenomegaly or gallstones. A total of 60 variants were identified, of which 46 (76.7%) were novel. The most frequently involved genes were ANK1 (28, 50.9%), SPTB (17, 30.9%), SLC4A1 (10, 18.2%), and SPTA1 (2, 3.6%). Patients aged ≤ 3 years (n = 23) showed significantly lower red blood cell counts, hemoglobin levels, and absolute reticulocyte counts than those aged > 3 years (n = 32) (all P < 0.05), whereas no significant phenotypic differences were observed across mutation types. Younger patients with HS exhibited more severe anemia. ANK1 and SPTB were the predominant pathogenic genes, with no notable phenotypic differences between these two genotypes. The identification of 46 novel mutations expands the mutational spectrum of HS.