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 .