Introduction
Hereditary spherocytosis is a common inherited disorder that is characterized by the presence of spheroidal erythrocytes on the peripheral blood smear. Its prevalence ranging from 1:2,000 to 1:5,000 in north European and 1:100,000 in Chinese individuals [1, 2]. The clinical manifestations of HS are variable, ranging from an asymptomatic condition to severe hemolysis. Typical HS patients present anemia, jaundice, splenomegaly and reticulocytosis [3]. In the neonatal period, the major clinical presents are jaundice and anemia. Splenomegaly and spherocytes are rarely observed [4]. Previous researches have shown that mutations of five genes that encode the erythrocyte membrane proteins are associated with HS, including ANK1, SPTB, SPTA1, SLC4A1, and EPB42, which result in a loss of membrane deformability and lead to surface area loss and an increased number of peripheral blood spherocytes [1]. Approximately 75% of HS cases are inherited in an autosomal dominant manner and a subset of patients show autosomal recessive inheritance or may carry a de novo mutation [5]. Blood transfusion and splenectomy are the main treatment to correct anemia and reduce clinical symptoms for HS patients.
The ANK1 gene is located at chromosome 8p11.2 and encodes several alternative splices. ANK1 mutations have been implicated in approximately half of all patients with hereditary spherocytosis (HS) [6], causing both dominant and recessive disease that can range from clinically mild and severe. ANK1 contains 42 exons that encode an 1,881 amino acid protein (referred to NM_000037.4), with three distinct domains: a N-terminal domain containing multiple ankyrin repeats; a center region with a spectrin-binding domain, and a C-terminal regulatory domain [7]. By linking β spectrin to band 3, ANK1 protein leads to spectrin assemble on the membrane and stabilize the blood cell membrane. NGS provides a comprehensive and cost-effective approach to molecular diagnosis of hereditary hemolytic anemia, including HS [8].
In this study, a heterozygous ANK1 c.856C>T mutation was identified by NGS and Sanger sequencing in a 2-hour-old newborn and his mother whom had been suffered anemia, jaundice and splenomegaly during her young time and received a splenectomy at the age of 12.
Results .