Characterization of a Novel 71.8 kb α⁰-Thalassemia Deletion and Subsequent Summary of a Practical Procedure for Thalassemia Molecular Diagnosis

Abstract

Thalassemia is the most common monogenic disorder around the world. Based on the principle of genotype–phenotype correlation, identification of thalassemia mutations is the essential prerequisite for clinical diagnosis and management. Because only common mutations are routinely detected, the identification of rare or undetermined mutations is a challenge for clinical laboratories. Herein, a proband presenting with inconsistent phenotype–genotype correlation after routine molecular screening was investigated by multiplex ligation-dependent probe amplification (MLPA), targeted-next generation sequencing (targeted-NGS), gap-polymerase chain reaction (gap-PCR) and Sanger sequencing. Eventually, a novel 71.8 kb deletion (– −^71.8) was identified and characterized, which included HBZ (ζ), HBA2 (α2), and HBA1 (α1) genes and was causing α⁰-thalassemia (α⁰-thal). Furthermore, we summarized a practical procedure based on accumulated experience in studies and clinical practice, which can be a guide for molecular screening and clinical diagnosis of thalassemia, especially for identification of undetermined or novel mutations.

Keywords:

• Genotyping
• novel deletion
• practical procedure
• targeted next-generation sequencing (targeted-NGS)
• thalassemia

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

This study was supported by the Guangdong Science and Technology Plan project [No. 2017A020214009], National Natural Science Foundation of China [No. 81972008], Medical Science and Technology Foundation of Guangdong Province [No. 20171011161954979].