δ-Globin Chain Variants Associated with Decreased Hb A₂ Levels: A National Reference Laboratory Experience

Abstract

High prevalence of hemoglobin (Hb) disorders mandates national programs for screening and genetic counseling in many countries. Increased Hb A₂ levels are commonly associated with β-thalassemias, however, various disorders including alteration of δ chains may result in decreased production of Hb A₂, thus hindering the diagnosis of β-thalassemias. The reported data reflect the experience of a large reference laboratory in the United States. In the current study, we have attempted to assess the prevalence and also tried to characterize the identified mutations in the HBD gene resulting in decreased Hb A₂ levels. In our cohort, 1.6% of 6486 patients were found to have Hb A₂ values of <1.9%. Bidirectional sequencing of the HBD gene demonstrated mutations in 20 cases (19.0% of the individuals with decreased Hb A₂). In addition to the previously reported variants, one novel mutation (Hb A₂-Utah or HBD: c.46T>C).

Keywords:

• Hb A₂
• HBD
• δ chain

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 research was performed at Associated Regional University Pathologists (ARUP) Laboratories, Salt Lake City, UT, USA.