First Report of the Spectrum of δ-globin Gene Mutations Among Women of Reproductive Age in Fujian Area-Discrimination of δ-thalassemia, α-thalassemia, and Iron Deficiency Anemia

Background: Low HbA level is an underlying of δ-thalassemia, α-thalassemia, and IDA. Interactions of these disorders can generate a wide spectrum of phenotype, which will pose diagnostic conundrum for clinical assessment, carrier screening, and genetic counseling.

Methods: Subjects with HbA levels below 2.0% with normal or reduced hematological parameters were recruited for further investigation. δ-globin gene mutations were identified by DNA sequencing of the HBD gene. Serum ferritin (SF) concentration was determined by the chemiluminescent microparticle immunoassay. The three common deletional α-thalassemia (-- /αα, -α /αα, and -α /αα) were detected using Gap-PCR, detection of the point mutations in the three nondeletional α-thalassemia (α α/αα,α α/αα,α α/αα), and the 17 common β-thalassemia was performed using reverse dot blot hybridization (RDB).

Results: We had characterized the δ-globin gene mutations in 20 cases, revealing a frequency of 0.4% in the women of reproductive age (20/4 792). Two previously known mutations:-77 T > C and -30 T > C and 3 novel δ-globin gene defects: -44G > A,CD87C > T, and CD134T > A were found. In the selected cases, we also found 85 cases confirmed with (51.2%,85/166) IDA and 39 cases (23.5%,39/166) with common α-thalassemia. Subjects with δ-thalassemia had statistically higher levels of Hb, MCV, and MCH compared with other two groups, whereas statistically lower levels of RDW were seen in δ-thalassemia group. What's more, statistically higher levels of SF were seen in δ-thalassemia group, compared with IDA groups.

Conclusion: We reported the spectrum of δ-thalassemia mutations for the first time with the frequency of 0.4% among women of reproductive age in Fujian area and found that -77T > C mutation was the most common mutation, followed by -30T > C mutation. What's more, 3 novel δ-globin gene defects: -44G > A,CD87C > T and CD134T > A were found. A thorough analysis of the hematological, electrophoretic characterization, and the level of SF was needed to suspect and further investigate the existence of IDA, α-thalassemia, and δ-thalassemia.