一个HPFH复合β地中海贫血家系的基因分析及其高危胎儿的产 …

目的 调查一种缺失型遗传性持续性肿儿血红蛋白综合征的基因型和表型的关系；探索进行β地中海贫血复合这种缺失型ＨＰＦＨ的高风险胎儿的快速产前诊断方法。方法 用跨越断裂点的三引物聚合酶链反应直接分析法检测ＨＰＦＨ缺失突变；用反向点杂交技术筛查β地贫基因突变。

Direct genotyping of an hereditary persistence of fetal hemoglobin deletion and rapid prenatal diagnosis of the fetus at-risk for compound heterozygote of this defect with beta-thalassemia in a Chinese family]

OBJECTIVE: To investigate the relationship between genotype and phenotype of a deletional hereditary persistence of fetal hemoglobin(HPFH) found in a Chinese family and explore an approach to rapid prenatal diagnosis for compound heterozygote of HPFH defects with beta-thalassemia. METHODS: By using the PCR-based method with three primers bridging a HPFH breakpoint and reverse dot blot (RDB) for detecting beta-thalassemia mutations, a Chinese family who had a propositus of six years old with intermediate thalassemia and requested prenatal diagnosis for the second pregnancy were screened. RESULTS: The propositus carried the HPFH deletion determinant inherited from her mother, and a codons 14-15 (+G) frameshift mutation causing beta-thalassemia from her father. Of six members in this family screened for this type of HPFH deletion, four were positive. Prenatal diagnosis of the fetus showed the same results as that of the propositus. An advice of termination of pregnancy was given and the result of prenatal diagnosis was confirmed in the DNA samples obtained after abortion. CONCLUSIONS: This is the first time to have performed prenatal diagnosis of Chinese family at-risk for compound heterozygotes for beta-thalassemia and HPFH in mainland China. The PCR assay for directly detecting the HPFH deletion is rapid and inexpensive and can be used as a routine in HPFH carrier screening and prenatal diagnosis.