Prevelence of α-Globin Deletions in β-Thalassemia Minor Patients and Differences in Erythrocyte Indices.

Introduction: β-thalassemia (thal) minor is caused by multiple β-globin (gb) gene mutations, most being located in the promotor and IVS-1. Large variations in erythrocyte indices between β-thal minor patients have been reported and are thought to be caused by the type of β-gb gene mutation. α-thal minor is caused by partial or total α-gb gene deletions. α-gb gene deletions have been reported in all racial origins. It is therefore likely that α-gb gene deletions occur in β-thal minor patients.This combination of gb genes mutations could also have an impact on erythrocyte indices.

Objectives: The trial objectives were to determine the prevalence of α-gb gene deletions in β-thal minor patients and to compare erythrocyte indices between 3 groups. Group 1: no α-gb gene deletion, Group 2: deletion of 1 α-gb gene, Group 3: deletion of 2 α-gb genes.

Methods: Diagnosis of β-thal minor was established using hemoglobin HPLC analysis (Variant II, Bio-Rad) with increased HbA2 +/− increased HbF without mutant Hb. The DNA of consecutive cases with newly diagnosed β-thal minor was extracted from leucocytes. A multiplex PCR assay was used to detect the presence of 7 α-globin gene deletions: −α^3.7,− α^{4.2, −− SEA, −− FIL, −− MED, −− THAI, −} α^20.5. Data on age, sex and erythrocyte indices (Hb, MCV, RBC and RDW) was recorded. An ANOVA was used to compare groups. P significance was established at 0.01 to adjust for multiple analysis.

Results: 300 specimen were collected in 9 months. 34 were excluded because of poor DNA quality or presence of a mutant Hb. 25 patients (9.4%) had at least 1 α-globin gene deletion. Group1 included 241 patients, Group 2: 20 patients and Group 3: 5 patients. No differences for age or sex were present between the groups. Differences in erythrocyte indices are reported in Table 1. LogMCV was used to adjust for variance heterogeneity.

Conclusions: 9.4% of β-thal minor have α-gb gene deletions. The only parameter that is significantly different between groups is MCV (Hb not reaching the pre-specified level of 0.01). It is therefore possible that differences in MCV between patients with β-thal minor can be explained by α-gb gene deletions. The concommittant presence of β-gb and α-gb mutations might improve the β-gb/α-gb imbalance implicated in ineffective erythropoiesis and a significant increase in MCV (and Hb but not reaching statistical significance in this study due to the sample size). However, this parameter does not have sufficient power to differenciate or identify β-thal minor patients with α-globin gene deletions. Other factors certainly influence MVC variability in β-thal minor patients and the independant influence of this variable (α-gb gene deletions) will require further investigation.

Erythrocyte indices between groups