非缺失型遗传性持续性胎儿血红蛋白综合征的研究

Hereditary persistence of fetal hemoglobin(HPFH) is a genetic condition characterized by persistence of fetal hemoglobin synthesis into adult life in the absence of signifcant hematological manifestations. They are now classified into deletional and non-deletional types. There are still many unknown mutations responsible for these defects. When HPFH co- inherited with thalassemia, it may develop to mild or severe anemia, and thalassemia is the most common genetic disease in Guangxi province.In this study, we will analyze the genotypes of nondeletional hereditary persistence of the fetal hemoglobin(HPFH) by polymerase chain reaction and DNA sequencing, and understand the mechanism involved in the high level of Hb F, the genotype and phenotype interaction betweem HPFH and thalassemia. The aim of the research is to provide basis and diagnostic mothods for genetic counselling and prenatal diagnosis, thus reducing the birth rate of thalassemia major and improving the quality of the population.

遗传性持续性胎儿血红蛋白综合征（HPFH）是一组以胎儿血红蛋白合成持续存在于成人而没有明显的血液学改变的综合征，分为缺失型与非缺失型。目前仍有许多未知的基因突变。当HPFH合并地中海贫血时，表现为轻至重度贫血。而地中海贫血是广西危害最严重的遗传性血液病。.本课题拟对遗传性持续性胎儿血红蛋白综合征（HPFH）携带者及病人，应用聚合酶链反应、基因测序等分子生物学方法进行研究，明确其基因突变类型及其分布；基因突变导致血红蛋白F水平升高的机制；及其合并β地中海贫血的基因型与临床表现型的关系等，建立相应的基因诊断方法，为地中海贫血的遗传咨询和产前基因诊断等提供理论依据和实施方法，从而降低重型地中海贫血患儿的出生率，提高人口素质。

本项目首次对大样本量的非缺失型遗传性持续性胎儿血红蛋白综合征（nd-HPFH）病例进行临床及基因分析。明确了中国人群nd-HPFH基因突变的主要类型，Hb F升高机制，其临床及血液学特征。阐明不同基因突变类型的nd-HPFH合并地中海贫血时，其对临床表现轻重程度和血液学特征的不同影响等。本项目的研究结果对nd-HPFH和地中海贫血的遗传咨询、诊疗和干预具有重要意义。