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

Abstract

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.

Keywords:

• Abnormal hemoglobin (Hb)
• β-globin gene
• frameshift mutation
• next generation sequencing (NGS)

Acknowledgements

We greatly appreciate Professor Xuan Shang’s (Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, PRC) helpful advice in writing this manuscript. We acknowledge the timely help given by Drs. Ning Liu and Huijun Li (Prenatal Diagnosis Center, Maternal and Child Health Care Hospital of Xinjiang, Uygur Autonomous Region, PRC) in re-obtaining the blood samples of the studied family. We also thank Xiaojun Wen and Huiling Xu (Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, PRC) for their assistance in conducting the paternal and maternal DNA tests for this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The study was supported by the the National Key R&D Program of China [2017YFC1001800], the Natural Science Foundation of China [31671314], Science and Technology Planning Project of Guangzhou [201604020045] and Natural Science Foundation of Guangdong Province [2017A030313673].