Research On The Mutation Of ~Aγ-196 C→T Causing Nondeletional Hereditary Persistence Of Fetal Hemoglobin

Objective To investigate the genotype and clinical features of non-deletio nal hereditary persistence of fetal hemoglobin (nd-HPFH) caused by Aγ196 C→T mutation on y-globin gene and co-inherited with β-thalassemia.Methods Cases admitted to the First Affiliated Hospital of Guangxi Med ical University from July 2014 to August 2015 were subjected to this study. Blo od cell counts and hemoglobin (Hb) analysis were conducted to the cases. DNA sequencing was performed for mutations on y-globin genes. While thalassemia mutations were analyzed by reverse dot blot hybridization(RDB) and gap-poly merase chain reaction (gap-PCR).Results1.Among 130 cases with elevated Hb F (Hb F≥4%),9 cases were identified as heterozygotes of Aγ196 C→T mutation. Five of these nine cases were simple heterozygotes of Aγ196 C→T mutation,all of them were adult female. While 2 cases were co-inherited with Aγ196 C→T mutation, including one adult male and one adult female.1 case was adult female co-inherited with Aγ196 C→T mutation and SEA deletional α-thalassemia.Another 1 case was adult female co-inherited with SEA de letional α-thalassemia.2. The heamatological examination of the five simple heterozygotes of Aγ196 C→T mutation showed that the Hb levels were from 104g/L to 132.7g/L, the mean corpuscular volume(MCV) from 81.1fL to 96.6fL, and the mean corp uscular hemoglobin(MCH) from 28.5pg to 33.4pg.2 cases co-inherited with Gγ 158 C→T mutation, the Hb level were 144g/L and 109.8g/L, MCV were 95fL and 95.05fL, MCH were 33pg and 32.15pg respectly. The case co-inherited with Gγ158 C→T mutation and SEA deletional a-thalassemia (--SEA/aa), heamatolo gical examination showed the Hb level was 117g/L; MCV was 77.9fL and MCH was 27.8pg. While the case co-inherited with SEA deletional a-thalassemia (--SEA/aa), its Hb level was 112g/L, MCV was 70.5fL and MCH was 22pg.3. Hb analysis showed that 5 simple heterozygotes of Aγ196 C→T mutation, Hb F were from 12% to 14%, Hb A2 were from 2.0% to 2.2%. The 2 cases co-inherited with Gγ158 C→T, Hb F were 16.9% and 16% respectively, Hb A2 were both of 1.9%. The case of Aγ196 C→T mutation combined with Gy-158 C→T and SEA deletional a-thalassemia (--SEA/aa) together, its Hb F was 12.9% and Hb A2 was 21.6%.4. Genetic analysis showed 9 cases were identified as heterozygotes of Aγ196 C→T mutation. Among these 9 cases,5 cases were simple heterozygotes of Aγ196 C→T mutation.2 case were co-inherited with heterozygotes of Gγ158 C→T mutation.1 case was co-inherited with heterozygotes of Gy-158 C→T mutation and SEA deletional a-thalassemia together.1 case was co-inherited with heterozygote of SEA deletional a-thalassemia.Conclusion1.The nondeletional hereditary peresistence of fetal hemoglobin resulting from the heterozygotes of Ay-196 C→T mutation has no clinical symptoms with normal blood test. The Hb analysis showed that Hb F is around 12%-16.9%.2. When the heterozygotes of Aγ196 C→T mutation co-inherited with SEA-thalassemia, it had no anemia but with lower MCV. This case is first reported.3. It is the first case that its Hb F levels was significantly higher than that of single mutation with Gγ158 C→T, when the heterozygotes of Aγ196 C→T mutation co-inherited with Gγ158 C→T mutation.