A Triple-Heterozygous β-Thalassemia Patient Demonstrated an Unusual Electrophoresis Pattern Due to a Novel β⁰ Mutation [an IVS-II-654 (C>T) mutation with a Hb Zürich-Langstrasse (HBB: c.151A>T) mutation in cis]

Abstract

β-Thalassemia (β-thal) is caused by mutations on the β-globin genes, causing reduced (β⁺) or absent (β⁰) synthesis of the β chains of hemoglobin (Hb). In this report, a 28-year-old male patient with anemia and jaundice, was diagnosed with triple-heterozygous β-thal [an IVS-II-654 (C>T) mutation, a Hb Zürich-Langstrasse (HBB: c.151A>T) mutation and a Hb G-Siriraj (HBB: c.22G>A) mutation] by gene sequencing. However, his electrophoresis pattern was unusual: 90.8% Hb G-Siriraj, 5.9% Hb A₂, 3.3% Hb F, no Hb A, no Hb Zürich-Langstrasse. His mother carried a β-thal trait (β^A/β^IVS-II-654) having mild anemia, with a classical electrophoresis pattern (95.1% Hb A, 4.4% Hb A₂, 0.5% Hb F). His father was heterozygous for Hb G-Siriraj (β^A/β^G-Siriraj) but asymptomatic, with a corresponding electrophoresis pattern (63.9% Hb A, 3.5% Hb A₂, 32.6% Hb G-Siriraj). In view of the family study results, the Hb Zürich-Langstrasse mutation in the proband was considered a de novo mutation occurring on the β^IVS-II-654 allele that he inherited from his mother, resulting in a β^{IVS-II-654/Hb Zürich-Langstrasse} genotype, which should be interpreted as a novel β⁰ mutation. This report illustrates that mutations in cis can confound genotype-phenotype correlations, therefore, just as DNA testing and Hb analysis, family study is also indispensable to the accurate identification of β-thal mutations.

Keywords:

• β-Thalassemia (β-thal)
• Hb G-Siriraj
• Hb Zürich-Langstrasse
• triple-heterozygous

Disclosure statement

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

Data availability statement

The complete data is available from the corresponding author. The data shall be shared on request.

Additional information

Funding

This study was supported by grants from the National Natural Science Foundation of China [81371878, 81902126].