Study For Homozygous ~Gγ-158C→T Mutation Resulting In Non-Deletional Hereditary Persistence Of Fetal Hemoglobin And Compounded With Thalassemia

Objective: To analysis the genotypes and clinical features of the ~Gγ-158C→T homozygous mutation resulting in non-deletional hereditary persistence of fetal hemoglobin(nd-HPFH)and the clinical features when compounded with thalassemia.Methods: All of Cases with Hb F level ≥4% were involved in this study from January to December 2016 at the First Affiliated Hospital Of Guangxi Medical University.Hematological examination were performed for the cases.Hemoglobin analysis were quantitated by high performance liquid chromatography(HPLC).Genotypes of thalassemia were quantitated by reverse dot blot hybridization(RDB)and gap-PCR.The mutations on γ-globin gene were analysis by DNA sequencing.Result:1.Among 90 cases with elevated levels of Hb F,5 cases were identified as homozygous ~Gγ-158 C→T mutation.The 5 cases included 3 children and 2adults.2.The result of the blood test: The 2 cases of homozygous ~Gγ-158 C→Tmutation showed that the Hb levels from 119.1 to 169.8 g/L,the mean corpuscular volume(MCV)from 79.18 to 95.36 fL,and the mean corpuscular hemoglobin(MCH)from 26.06 to 32.95 pg.The 2 cases of homozygous mutation combined with α-thalassemia showed that the Hb levels from 96 to107.7 g/L,MCV from 66.1 to 62.63 fL,and MCH from 19 to 19.56 pg.The case of homozygous mutation co-inherited with β-thalassemia showed that the Hb levels were 101 g/L,MCV were 69.1 fL,and MCH were 23.7 pg.3.The result of Hemoglobin analysis: The 2 cases of homozygous ~Gγ-158C→T mutation showed that the Hb F levels from 4 to 5.1%,the Hb A2 levels from 1.5 to 2.8 %.The 2 cases of homozygous mutation combined withα-thalassemia showed that the Hb F levels from 4.0 to 4.1%,the Hb A2 levels from 2.6 to 2.8%.The case of homozygous mutation co-inherited withβ-thalassemia showed that the Hb F levels were 97.3 %,the Hb A2 levels were2.6 %.4.The result of genetic analysis: 5 cases were identified as homozygous ~Gγ-158 C→T mutation.In which,2 cases were compounded with α-thalassemia,Hb Constant Spring and SEA deletional α-thalassemia respectively.And 1 case compounded with β-thalassemia(βCD27/28/βN).Conclusion:1.Homozygous ~Gγ-158 C>T mutation on γ-globin gene may cause nd-HPFH.It had no obvious clinical symptoms,but with elevated Hb F level,normal or decreased Hb A2 level,normal or lower level of Hb,MCV and MCH.2.When homozygous ~Gγ-158 C>T mutation compounded withα-thalassemia,the Hb F level were elevated which was similar to those of simple homozygous mutation cases,but Hb,MCV and MCH were more lower.3.When homozygous ~Gγ-158 C>T compounded with β-thalassemia,it ledto normal level of Hb A2,significantly elevated Hb F and normal or lower level of Hb,MCV and MCH.This suggested it is easy to misdiagnose without genetic analysis.