Clinical Genotyping by Next Generation Sequencing Reveals a Novel, De Novo β-Globin Gene Mutation Causing Hemolytic Anemia in a Chinese Individual

Abnormal hemoglobins (Hbs) are one of the most common hemoglobinopathies worldwide. Some Hb gene mutations may produce unstable, abnormal Hbs causing macrocytic hemolysis. We identified a novel, de novo deletion/frameshift mutation at nucleotide position 408 in exon 3 of the β-globin gene (HBB: c.408delT) compound with an Hb F-associated regulatory single nucleotide polymorphism (rSNP) (rs368698783) through next generation sequencing (NGS). This β-globin gene variant was identified in a 5-year-old Chinese girl with splenomegaly, jaundice and macrocytic, hemolytic anemia. This variant causes a new stop codon to be formed in the 3' untranslated region (3'UTR) of the HBB gene at amino acid position 158, consequently leading to a β-sheet disruption of the last α helix of this abnormal β-globin chain. We named this variant Hb Urumqi after the proband's current city of residence.