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(2)level is an underlying of delta-thalassemia, alpha-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(2)levels below 2.0% with normal or reduced hematological parameters were recruited for further investigation. delta-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 alpha-thalassemia (--(SEA)/alpha alpha, -alpha(3.7)/alpha alpha, and -alpha(4.2)/alpha alpha) were detected using Gap-PCR, detection of the point mutations in the three nondeletional alpha-thalassemia (alpha(CS)alpha/alpha alpha,alpha(QS)alpha/alpha alpha,alpha(WS)alpha/alpha alpha), and the 17 common beta-thalassemia was performed using reverse dot blot hybridization (RDB). Results: We had characterized the delta-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 > Cand-30 T > Cand 3 novel delta-globin gene defects:-44G > A,CD87C > T,andCD134T > Awere 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 alpha-thalassemia. Subjects with delta-thalassemia had statistically higher levels of Hb, MCV, and MCH compared with other two groups, whereas statistically lower levels of RDW were seen in delta-thalassemia group. What's more, statistically higher levels of SF were seen in delta-thalassemia group, compared with IDA groups. Conclusion: We reported the spectrum of delta-thalassemia mutations for the first time with the frequency of 0.4% among women of reproductive age in Fujian area and found that-77T > Cmutation was the most common mutation, followed by-30T > Cmutation. What's more, 3 novel delta-globin gene defects:-44G > A,CD87C > TandCD134T > Awere 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, alpha-thalassemia, and delta-thalassemia.