非缺失型遗传性持续性胎儿血红蛋白综合征的研究

RESEARCH ON NON-DELETIONAL HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN

目的:探讨广西地区非缺失型遗传性持续性胎儿血红蛋白综合征(non-deletional hereditary persistence of fetal hemoglo-bin,nd-HPFH)的基因突变和临床表型特点。方法:对2011年12月至2012年6月在广西医科大学第一附属医院就诊的患者进行血常规检测;应用高效液相色谱法进行Hb分析;应用DNA测序方法分析g珠蛋白基因突变;用反向斑点杂交和Gap-PCR方法检测地中海贫血基因突变。结果:在胎儿血红蛋白(Hb F)增高的病例中检测出6例Ag-158C→T突变杂合子,其中有5例合并Gg-158C→T突变,1例同时伴有杂合子β地中海贫血CD 41/42突变,1例伴有-α3.7缺失型α地中海贫血。血常规检测显示6例病例的Hb为108～129g/L,MCV 66.4～85.4fL,MCH为23.4～30.7pg。血红蛋白分析结果显示Hb F均升高,为4%～18%。5例Hb A2正常,1例复合β地中海贫血杂合子的Hb A2为5.7%。结论:首次在中国人群中检出Ag-158C→T突变导致nd-HPFH,其杂合子无临床症状,Hb F升高,血常规正常或MCV、MCH降低。当合并杂合子β地中海贫血或α地中海贫血时,MCV,MCH降低。

Objective： To investigate the genotype and clinical features of non-deletional hereditary persist- ence of fetal hemoglobin syndrome in Guangxi. Methods： Cases admitted to the First Affiliated Hospital of Guangxi Medical University from December 2011 to June 2012 were subjected to this study. Blood cell counts, hemoglobin analyses by high performance liquid chromatography （HPLC） were performed in the cases. Genotypes were analyzed by reverse dot blot hybridization （RDB）, gap-PCR and DNA sequencing. Results： Among the cases with elevated levels of Hb F, 6 were identified as heterozygote Ag-158 C-T mutation. While 5 cases accompanied by Gg -158 C-T mutation, 1 with b-thalassemia CD 41/42 mutation, and 1 with-a3.7 deletional a-thalassemia. The haematological examination showed the Hb level from 108 g/ L to 129 g/L, mean corpuscular volume （MCV） level from 66.4 to 85.4 fL and mean corpuscular hemoglobin （MCH） from 23.4 to 30.7 pg. Hemoglobin analysis showed elevated Hb F around 4%-18%. Hh A2 was normal in 5 cases but was 5.7% in 1 case with heterozygote β-thalassemia. Conclusion： This is the first report in Chinese that non-deletional hereditary persistence of fetal hemoglobin syndrome resulted from Ag -158 C-T mutation. The heterozygotes have no clinical symptoms, but have elevated Hb F level, normalhaematological examination or lower MCV and MCH. When coinherited with β-thalassemia or a- thalassemia, they also have lower MCV and MCH.