The study population included 61,796 subjects who underwent a diagnosis of thalassemia. Among these, we collected 309 DNA samples that conformed to the aforementioned conditions. Of the 309 samples, eight were identified as α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutations (Fig. 1), including one pedigree, and of these, four had coinheritance with - -SEA deletion. The hematological parameters of samples from individuals with the α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation are presented in Table 1.
P1 (Table 1) was known to have moderately severe anemia and jaundice, and was transferred to the neonatology department for therapy at the local hospital. Afterwards, he was referred to us for further investigation at the age of three months. A molecular analysis of the α-globin genes revealed the genotype of αcodon 30 (-GAG)α/- -SEA. When he was two and a half years old, he was diagnosed with developmental disorders of speech and language and mild growth retardation. He was asked to undergo a rehabilitation of speech and language and follow-ups. His mother was a carrier of α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation (P8, Table 1).
P2 (Table 1) was known to have been pale since birth, and a diagnosis of mild α-thal was made at a regional hospital when he was two months old. At the age of six, he was referred to our pediatrics out-patient clinic because of cough and recurrent fever due to unknown causes, whereafter he was admitted to the hospital for therapy. He had moderately severe anemia, jaundice, but no hepatosplenomegaly. When he was in hospital, his anemia worsened with his hemoglobin level reducing from 79 g/dL to 68 g/dL in only three days. Then, he underwent a further investigation of thalassemia. Using a molecular analysis, the patient was found to have a compound heterozygote of - -SEA and α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation; thus, he was diagnosed with Hb H disease. Subsequently, he received blood transfusion with his parents’ informed consent. With blood transfusion, his anemia improved, and the hemoglobin level increased to 114 g/dL. The next day, he was discharged from the hospital with improvement after treatment. He has to report back for a further follow-up.
P3 (Table 1) was an adult male who had mild hypochromic microcytic anemia. He was known to have been pale since birth, and a diagnosis of Hb H disease was made during his partner’s pregnancy examination for thalassemia. His physical and mental development was normal, except for mild anemia. He did not require a blood transfusion.
P4 (Table 1) presented with anemia, and a tentative diagnosis of iron-deficiency anemia was made. She had received few blood transfusions occasionally to correct the symptoms of anemia in the absence of a definitive diagnosis. At the age of 23, she was referred to us, and a definitive diagnosis of Hb H disease was made. She had mild anemia and iron overload with serum ferritin increasing to the level of 350.6 ng/mL.
P5 (Table 1) had mild anemia like the carrier of - -SEA, and P6, P7, and P8 (Table 1) had erythrocyte microcytosis. All the four patients’ medical histories were not special.
Heterozygote for α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation
A total of 43 carriers with α-globin gene mutations and 30 healthy individuals were enrolled as control in the present study, while three carriers with the α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation were enrolled as experimental group. Among the 43 carriers with α-globin gene mutations, 30 had αQSα mutation; and the rest (n = 13) had the α2 codon 30 (GAG>CAG) (HBA2: c.91G>C) mutation (Table 2). Within the experimental group, all the carriers were found had erythrocyte microcytosis, they had significantly lower levels of MCV and MCH than those with the heterozygous α2 codon 30 (GAG>CAG) (HBA2: c.91G>C) mutation and healthy individuals (p < 0.01). However, there were no statistically significant differences on hematological indices between the carriers with the α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation and αQSα mutation (p > 0.05).
Compound heterozygous of - -SEA and α2 codon 30 (-GAG) (HBA2: c.91_93delGAG) mutation
A total of 56 α-thalassemic and four patients with α codon 30 (-GAG) α/- -SEA genotype were enrolled as control and experimental group in the present study, respectively. Within the control group, there were 20 patients with αQSα/- -SEA genotype; and 36 patients with - -SEA/αα genotype (Table 3). Within the experimental group, their Hb and MCH levels were significantly lower than that of control group with - -SEA/αα genotype (p < 0.01). Between the patients with α codon 30 (-GAG) α/- -SEA genotype and αQSα/- -SEA genotype, the values of hematological indices were compared and found no statistically significant differences (p > 0.05).