| Objectives:To investigate the genotype and clinical features of non-deletional hereditary persistence of fetal hemoglobin(nd-HPFH)in compound with p-thalassemia.Methods:Cases admitted to the First Affiliated Hospital of Guangxi Medical University from June 2013 to July 2014 were subjects in this study.Hematological examination were performed.Hb F and Hb A2 were measured by high performance liquid chromatography(HPLC).Genotypes were analyzed by DNA sequencing,reverse dot blot hybridization(RDB)and gap-polymerase chain reaction(gap-PCR).The data were processed by SPSS 16.0 statistical software.30 normal persons were served as control group for DNA sequencing of ? globin gene,while 40 ?-thalassaemia heterozygotes were also set as control groups.Results:1.Among the 122 cases with elevated Hb F,7 cases were identified as A?-225 to-222 deletion,including 5 childen and 2 adults.And in this group 3 cases were in compound with G?-158 C?T mutation,and 2 with ?-thalassemia.26 cases were identified as G?-158 C?T mutation,including 15 childen and 11 adults.In which 4 were in compound with A?-158 C?T mutation,and 12 with?-thalassemia.2.All of 7 heterozygotes of A?-225 to-222 deletion(while 2 in compound heterozygosity with ?-thalassemia)had no clinical symptoms.26 heterozygotes of G?-158 C?T mutation had no clinical symptoms or had mild to moderate anemia.The clinical symptoms of 12 compound heterozygotes of G?-158 C?T mutation with ?-thalassemia were different,for 9 had no clinical symptoms or had mild anemia,and 3 showed moderate anemia.3.The hematological examination showed that 7 heterozygotes of A?-225 to-222 deletion had the hemoglobin(Hb)levels ranged from 96.7 to 142.3 g/L,mean corpuscular volume(MCV)54.61 to 77.65 fl and mean corpuscular hemoglobin(MCH)16.10 to 25.26 pg.And in this group 3 compound heterozygotes of A?-225 to-222 deletion with G?-158 C?T mutation showed Hb levels from 104.3 to 142.3 g/L,MCV levels from 59.41 to 77.65 fl and MCH levels from 17.79 to 25.26 pg.And 2 compound heterozygotes of A?-225 to-222 deletion with ?-thalassemia showed Hb levels from 119.3 to 142.3 g/L,MCV levels from 64.19 to 76.49 fl and MCH levels from 19.40 to 24.79 pg.26 heterozygotes of G?-158 C?T mutation had Hb levels from 84.3 to 140.3 g/L,MCV levels from 57.38 to 115.90 fl and MCH levels from 16.91 to 39.11 pg.In which 4 compound heterozygotes of G?-158 C?T with A?-158 C?T showed Hb levels from 97.0 to 140.3 g/L,MCV levels from 64.10 to 100.90 fl and MCH levels from 20.40 to 32.69 pg.And 12 compound heterozygotes of G?-158 C?T with ?-thalassemia showed Hb levels from 84.3 to 125.3 g/L,MCV levels from 57.38 to 71.87 fl and MCH levels from 16.91 to 22.72 pg.10 heterozygotes of ?-thalassaemia(-28 A?G)showed Hb levels from 95.5 to 143.6 g/L,MCV levels from 67.35 to 76.48 fl and MCH levels from 21.09 to 23.81 pg.10 heterozygotes of ?-thalassaemia(CD 17 A?T)showed Hb levels from 84.9 to 119.6 g/L,MCV levels from 56.90 to 70.21 fl and MCH levels from 17.38 to 21.76 pg.10 heterozygotes of P-thalassaemia(CD41/42(-TTCT))showed Hb levels from 93.0 to 115.3 g/L,MCV levels from 57.90 to 66.22 fl and MCH levels from 17.56 to 20.70 pg.10 heterozygotes of?-thalassaemia(IVS-?-654 C?T)showed Hb levels from 81.0 to 131.9 g/L,MCV levels from 55.32 to 69.96 fl and MCH levels from 16.56 to 21.57 pg.4.The hemoglobin analysis showed 7 heterozygotes of A?-225 to-222 deletion had Hb F ranging from 4.0%to 11.2%.While 3 compound heterozygotes of A?-225 to-222 deletion and G?-158 C?T had Hb F ranging from 4.0%to 8.1%,and 2 compound heterozygotes for A?-225 to-222 deletion and ?-thalassemia had Hb F ranging from 8.1%to 11.2%.The Hb A2 levels were normal in 5 heterozygotes of A?-225 to-222 deletion,but were increased in 2 compound heterozygotes for A?-225 to-222 deletion and ?-thalassemia(ranging from 5.6%to 6.4%).26 heterozygotes of G?-158 C?T mutation had Hb F ranging from 4.3%to 14.0%.While 4 compound heterozygotes for G?-158 C?T and A?-158 C?T mutation had Hb F ranging from 5.7%to 9.8%,and 12 compound heterozygotes of G?-158 C?T with ?-thalassemia had Hb F ranging from 5.7%to 14.0%.The Hb A2 levels were normal in 15 heterozygotes of G?-158 C?T mutation,but were increased in 11 compound heterozygotes of G?-158 C?T with?-thalassemia(ranging from 4.5%to 5.7%).10 heterozygotes of ?-thalassaemia(-28 A?G)had Hb F ranging from 0.9%to 3.1%.10 heterozygotes of ?-thalassaemia(CD17 A?T)had Hb F ranging from 0.3%to 3.1%.10 heterozygotes of ?-thalassaemia(CD41/42(-TTCT))had Hb F ranging from 0.4%to 3.4%.10 heterozygotes of?-thalassaemia(IVS-?-654 C?T)had Hb F ranging from 0.6%to 3.3%.5.The genetic analysis identified 7 heterozygotes of Ay-225 to-222 deletion,while 3 were in compound heterozygosity with G?-158 C?T mutation,1 with?-thalassemia-28 A?G mutation,1 with ?-thalassemia CD17 A?T mutation.It also identified 26 heterozygotes of G?-158 C?T mutation,while 4 were in compound heterozygosity with A?-158 C?T mutation,2 with ?-thalassemia CD 17 A?T mutation,8 with ?-thalassemia CD41/42(-TTCT)mutation,2 with ?-thalassaemia IVS-?-654 C?T mutation.6.The Hb F and Hb levels of the compound heterozygotes for A?-225 to-222 deletion and ?-thalassemia showed statistically significant difference(P<0.05)comparing with those of ?-thalassaemia heterozygotes.Comparing the two groups,compound heterozygotes of G?-158 C?T with ?-thalassemia and?-thalassaemia heterozygotes,there were statistically significant difference in Hb F levels(P<0.05)and no statistically significant difference in Hb levels(P>0.05).Conclusions:1.This is the first report about Ay-225 to-222 deletion associated with nd-HPFH and A?-225 to-222 deletion in compound with ?-thalassemia in Chinese population.2.The heterozygotes of A?-225 to-222 deletion had increased Hb F levels,normal or lower Hb levels,lower MCV and MCH,and no clinical symptoms.3.The compound heterozygotes for A?-225 to-222 deletion and?-thalassemia had no clinical symptoms,increased Hb F levels,normal Hb levels,lower MCV and MCH.They had higher Hb F and Hb levels than those of?-thalassaemia heterozygotes..4.The heterozygotes of G?-158 C?T mutation had increased Hb F level,normal or lower Hb,MCV and MCH.They had no clinical symptoms or had mild to moderate anemia.5.The compound heterozygotes for G?-158 C?T mutation and?-thalassemia had no clinical symptoms or had mild to moderate anemia,increased Hb F levels,normal or lower Hb levels,lower MCV and MCH.Comparing to ?-thalassaemia heterozygotes,they had higher Hb F levels,but had no statistically significant difference in Hb levels. |
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