De novo mutations in ANK1 and SPTB cause hereditary spherocytosis: three case reports and literature review

Hereditary spherocytosis (HS) is characterized primarily by jaundice, anemia, splenomegaly (enlarged spleen), increased numbers of spherocytes in peripheral blood, and elevated erythrocyte osmotic fragility. However, these manifestations are nonspecific, resulting in misdiagnosis or underdiagnosis. Here, we report three Chinese patients with a family history of HS. Case 1 was an infant who presented with jaundice and anemia during the neonatal period, without splenomegaly; case 2 was a woman with hepatitis C and mild anemia; and case 3 was a child with no obvious clinical symptoms. Genetic testing revealed a heterozygous ANK1 c. 4429 C > T (p. Arg1477*) de novo mutation in case 1, a heterozygous ANK1 c. 1025₁028dup (p. Val344Profs*13) de novo mutation in case 2, and a heterozygous SPTB c. 5898 C > T (p. Gly1966 =) de novo variant in case 3. Interestingly, to the best of our knowledge, the ANK1 c. 4429 C > T (p. Arg1477*) and c. 1025₁028dup (p. Val344Profs*13) de novo mutations have not been previously reported in public mutation databases, extending the mutation spectrum of ANK1. Overall, HS should be considered in patients with unexplained jaundice or anemia, even in those without a family history. Clinicians should conduct genetic testing to establish a definitive diagnosis, guide treatment modalities, and provide genetic counseling to patients.