Hereditary spherocytosis (HS) is a common inherited heterogeneous hemolytic anemia that is characterized by the presence of spheroidal erythrocytes on the peripheral blood smear. Mutations in ankyrin gene (ANK1) is the most common cause of HS in Northern European populations and Chinese patients but is seen in only 5–10% of Japanese patients. The majority of them are familial mutations inherited in an autosomal dominant form. In this study, a heterozygous ANK1 c.856C>T mutation was identified in a 2-hour-old newborn with severe jaundice using targeted next-generation sequencing (NGS) and Sanger sequencing, and was confirmed to be inherited from his mother.

A novel heterozygous mutation (c.325dup) was identified in EXT1 gene from the proband and the affected family members; this mutation was absent in all the unaffected family members. The identification of the novel frameshift insertion mutation (c.325dup) expands the mutation spectrum of HME, which provides new evidence for HME diagnosis.

The Duchenne Muscular Dystrophy (DMD) gene variants are associated with the disease phenotypes. The pathogenic mutation, c.2293-1G>C, was detected in DMD gene in the proband and the fetus, which has not been reported in the literature.The minigene expression in vitro confirmed that c.2293-1G>C is responsible of aberrant splicing.