A novel ANK1 gene mutation associated with hereditary spherocytosis: a case report

Hereditary spherocytosis (HS) is an inherited form of hemolytic anemia resulting from defects in the red blood cell membrane skeleton. Its classic clinical presentation includes anemia, jaundice, and splenomegaly. Key laboratory findings that support the diagnosis are the presence of spherocytes and an elevated reticulocyte count on peripheral blood smear.

An 8-year-old girl presented with a longstanding history of jaundice-noted for four years-affecting both her skin and sclera. She also reported intermittent episodes of tea-colored urine. Physical examination revealed hepatosplenomegaly. Laboratory investigations demonstrated normocytic anemia, a positive osmotic fragility test, and the presence of spherocytes on peripheral blood smear, which was subsequently confirmed by electron microscopy. Whole-exome sequencing identified a novel heterozygous pathogenic mutation (c.2388 + 2T > A) in the ANK1 gene (NM_000037.4, Intron). This splice-site mutation leads to aberrant splicing, causing a frameshift and introduction of a premature termination codon (PTC), likely triggering nonsense-mediated mRNA decay (NMD) and resulting in a truncated, dysfunctional Ankyrin-1 protein.

This study reports a novel ANK1 mutation (c.2388 + 2T > A) identified in a Chinese patient with hereditary spherocytosis. Located at a critical splice donor site, this previously unreported variant is predicted to cause disease through the inclusion of a cryptic exon. The finding provides new insight into the genetic basis of HS in the Chinese population.