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Semi-Nested Taqman Real-Time Quantitative PCR for Noninvasive Prenatal Diagnosis of Bart’s Hydrops Fetalis

Sakorn Pornprasert PhD*, Kanyakan Sukunthamala BSc**, Naowarat Kunyanone MSc***, Sririchai Sittiprasert MSc***, Khanungnit Thungkham MSc****, Sumeth Junorse BSc****, Khachonsilp Pongsawatkul MD****, Wisut Pattanaporn MD**, Chantip Jitwong MD*****

Affiliation : * Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand ** Health Promoting Hospital Chiang Mai, Chiang Mai, Thailand *** Chiang Rai Hospital, Chiang Rai, Thailand **** Phayao Hospital, Phayao, Thailand ***** Lamphun Hospital, Lamphun, Thailand

Background : Non-invasive prenatal diagnosis based on detection of fetal cell-free DNA is limited when mother and father are both carriers for the same autosomal recessive mutation.
Objective : Develop the semi-nested Taqman real-time PCR for quantification of α-thalassemia-1 SEA type deletion allele in plasma of α-thalassemia-1 SEA carriage pregnancies. Material and Method: Plasma DNA was extracted from six women who carried fetuses with normal, 11 with heterozygote α-thalassemia-1 SEA type deletion and seven with Bart’s hydrops fetalis. DNA was amplified using conventional PCR with the primary specific primer set for α-thalassemia-1 SEA type deletion. PCR product was then subjected to the semi-nested real- time PCR using the secondary specific primer and Taqman probe set for α-thalassemia-1 SEA type deletion. The standard curve was constructed using ten-fold serial dilutions of conventional PCR product of the heterozygote α-thalassemia-1 SEA type deletion.
Results : Women who carried fetuses with Bart’s hydrops fetalis displayed a trend toward higher mean copy number of α-thalassemia-1 SEA type deletion allele vs. women who carried fetuses with normal and heterozygote, albeit not reaching statistical significance.
Conclusion : The maternally inherited fetal allele present in maternal plasma is difficult to discern the fetal cell-free DNA from a higher background DNA of the mother. Thus, further investigation is needed to improve the diagnosis of Bart’s hydrops fetalis using this technique.

Keywords : α-thalassemia-1 SEA type deletion, Fetal cell-free DNA, Prenatal diagnosis, Semi-nested real-time PCR, Taqman probe


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