Identification of a novel pre-terminating mutation in human HBB gene as a cause of β0-thalassemia phenotype.

Abstract

Beta (β)-thalassemia (thal) is one of the most common genetic disorders of hemoglobin synthesis worldwide. Most cases of β-thal are caused by point mutations in hemoglobin subunit beta (HBB) gene, and only a minority of cases are caused by missing mutations of HBB gene. In this study, a 31-year-old pregnant woman with a typical thal phenotype was admitted at Fujian Provincial Maternity and Children's Hospital for prenatal diagnosis. Her father also presented with a typical thal phenotype, while the other members in the proband family were normal. Interestingly, Gap-PCR and reverse dot-blot hybridization assays showed that no mutation was found in the human HBA and HBB genes of the proband and her father. Subsequently, Sanger DNA sequencing identified a novel pre-terminating mutation, c.271 G>T [CD90 (GAG>TAG, Glu→stop codon)], in HBB gene from the proband and her father, while the other members in the proband family were normal. This mutation created a stop codon at amino acid 90 in exon 2 coding sequences of HBB gene, and led to a β0-thal phenotype. In summary, the present study is, to the best of our knowledge, the first to report a pre-terminating mutation, c.271 G>T [CD90 (GAG>TAG, Glu→stop codon)], in human HBB gene as a cause of β0-thal phenotype. This is important for clarifying the molecular mechanism of β0-thal and is useful for genetic counseling and prenatal screening.

• Authors: Liangpu Xu, Meihuan Chen, Hailong Huang, Na Lin, Lingji Chen, Yan Wang, Min Zhang, Deqin He, Yuan Lin
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 12 Issue 8 Pg. 3070-3076 ( 2019) ISSN: 1936-2625 [Electronic] United States
• PMID: 31934147 (Publication Type: Case Reports)
• Copyright: IJCEP Copyright © 2019.