Initation Coden Mutation Of ?2-Globin Gene Causing ?-Thalassemia

Objectives:To analyse the genotype and hemotologic characterization of Hb H disease.Methods:203 cases diagnosed as Hb H disease by hemalogic and hemoglobin analysis at The First Affiliated Hospital of Guangxi Medical Univeristy from April 2015 to December 2015, were the subjects in this study. a-Thalassemia mutations were analyzed by gap-polymerase chain reaction (gap-PCR), reverse dot blot hybridization (RDB) and DNA sequencing. Data were analysed by SPSS 17.0 statistical software.Results:1. An uncommon case with nondeletional Hb H disease was found among the 203 cases. The proband was a 30 years old male, who had no jaundice, no hepatosplenomegaly, and did not receive blood transfusion. His hemotologic data showed Hb 87g/L, RBC 4.57×1012L, MCV 67.7fL, MCH 19pg, MCHC 304.40g/L and HCT 0.285. Hemoglobin analysis showed Hb H+Hb Bart's 26.6%, Hb A2?1.5%, and Hb F 0.7%. DNA sequencing confirmed the genotype of the proband was an initation coden mutation (ATG?A-G) on ?2-globin gene and combined with SEA a-Thalassemia-1 mutation. Family survey suggested that the father, whose blood routine examination and Hb analyse were normal. DNA sequencing showed the father was a heterozygote for the initation coden mutation (ATG?A-G) of a2-globin gene. The mother was heterozygote of SEA a-Thalassemia-1 (-SEA/aa), withHb 111g/L, RBC4.9×1012 L, MCV 69.4f L, MCH 22.6pg, MCHC 326g/L and HCT 0.341.2.109 cases of deletional Hb H disease were detected, accounting for 53.5%. These cases included 73 cases of?--SEA/-?3.7 (35.9%),35 cases of__SEA/_?4.2 (17.2%),1 case of-THAI/-a4.2. Another 87 cases were diagnosed as nondeletional HbH disease, including 87 cases of?--SEA/?cs?,4 cases of-SEA/?QS?,1 case of--THAI/?ca?,1 case of--SEA/?A30? and 1 for --SEA/?ATG?A-G? respectively.3.8 types of alleles were discovered. Dtetction rate of allele of -SEA was 99%, followed by allele acsa, allele -?3.7, allele -?4.2 and allele aQsa. Allele-THAI, allele ??30? and allele ?ATG?A-G? were uncommon.4. Mean Hb H level of deletional Hb H group and nondeletional Hb H disease group were compared, Hb H-CS group had the highest level of Hb H, followed by Hb H-QS group. There was no statistical significance between these two groups (P>0.05).--SEA/-?42 group had a mean Hb H level of (12.3±3.4)%, while--SEA/-?3.7 group had lowest mean Hb H level of (10.3±3.9)%. There has statistical significant difference between these two groups (P<0.001)5. Comparing the hematology parameters between the deletional Hb H disease group and nondeletional Hb H disease group, nondeletional Hb H disease group had lower level of Hb, but higher level of MCV and MCH than that of deletional Hb H disease group. There had statistical significant difference between the two groups (P<0.001)Conclusions:1. Initiation coden mutation of a2-globin gene causes a-Thalassemia. The heterozygote has no clinical symptoms with normal hematologic parameters and Hb analyses. When co-inheritied with SEA a-Thalassemia-1, it may lead to Hb H disease with moderate anemia. This initation coden mutation is easily to be missed, and only can be confirmed by DNA analysis.2. --SEA/? a are the most common genotype for Hb H disease in Guangxi Province, followed by--SEA/-?3.7,--SEA/-?4.2 and--SEA/?QS? genotypes.3. Allele of --SEA is the most prevelent. Followed by allele acsa, allele-?3.7, allele-?4.2 and allele ?QS?.4. Patients with nondeletional Hb H disease have more severer anemia, but a higher level of MCV and MCH than that of deletional Hb H disease.