BACKGROUND:

Noninvasive prenatal diagnosis based on detection of fetal cell-free DNA is hampered when mother and father are both carriers for the same autosomal recessive mutation.

OBJECTIVE:

To compare the diagnosis of Bart's hydrops fetalis using conventional Gap-PCR analysis of fetal cells/tissues with the measurement of quantitative difference (deltaCp) between alpha-thalassemia-1 SEA type deletion gene (C(T-mutant)) and wild type alpha-globin gene (C(T-wild type)) in plasma of pregnancies by using the Taqman real-time quantitative PCR.

MATERIAL AND METHOD:

Plasma DNA samples were collected from three groups of pregnancies whose fetuses have known thalasemia status (7 normal, 11 heterozygote alpha-thalassemia-1 SEA type deletion, and 7 Bart's hydrops fetalis). The alpha-thalassemia-1 SEA type deletion gene and wild type alpha-globin gene were quantified by using Taqman real-time quantitative PCR and then the delta C(T) was analyzed by subtracting the C(T-mutant) from C(T-wild type).

RESULTS:

Mean deltaC(T) values were not significantly different among the three groups. However, women whose fetuses were diagnosed as Bart's hydrops fetalis had a higher proportion (43%) of plasma DNA samples that had negative deltaC(T) value than women whose fetuses were diagnosed as normal or heterozygote alpha-thalassemia-1 SEA type deletion (0 and 27%, respectively).

CONCLUSION:

Further investigations are needed to improve the diagnosis of Bart's hydrops fetalis using fetal cell-free DNA.