Noninvasive prenatal diagnosis experience in the Çukurova Region of Southern Turkey: detecting paternal mutations of sickle cell anemia and β-thalassemia in cell-free fetal DNA using high-resolution melting analysis

Prenat Diagn. 2013 Nov;33(11):1054-62. doi: 10.1002/pd.4196. Epub 2013 Aug 23.

Abstract

Objective: This study used a high-resolution melting (HRM) technique to detect paternal mutations for the noninvasive prenatal diagnosis (NIPD) of β-thalassemia and sickle cell anemia (HbS). We also determined the levels of cell-free fetal DNA and total cell-free DNA.

Methods: We used the HRM technique for fetal genotyping of paternal mutations in maternal plasma from 32 pregnancies at risk of β-thalassemia and 57 pregnancies at risk of HbS. The DNA levels in maternal plasma were measured using real-time quantitative PCR. Multiples of the median (MoM) values were calculated in women at risk for β-thalassemia or HbS.

Results: Twenty-two paternal mutations were detected in 89 pregnant women. Although we were successfully able to detect the paternal β-thalassemia mutations, the mutant HbS fetuses could not be distinguished from maternal background in the early weeks of pregnancy. The detection of DYS14 in male fetuses was 100%. The MoM values of women at high risk of having HbS-affected fetuses were higher than those for the other groups.

Conclusion: High-resolution melting is a useful method for NIPD of β-thalassemias by detecting paternal mutations in the maternal plasma. Cell-free fetal DNA quantification and MoM values were not informative for HbS or β-thalassemias in early pregnancy.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / diagnosis*
  • Anemia, Sickle Cell / genetics
  • Cell-Free System
  • DNA / analysis
  • DNA / metabolism
  • DNA Mutational Analysis / methods*
  • Fathers
  • Female
  • Fetus / metabolism
  • Genetic Testing / methods*
  • Humans
  • Male
  • Maternal Serum Screening Tests / methods
  • Nucleic Acid Denaturation / genetics
  • Polymerase Chain Reaction / methods
  • Pregnancy
  • Prenatal Diagnosis / methods*
  • Turkey
  • Young Adult
  • beta-Thalassemia / diagnosis*
  • beta-Thalassemia / genetics

Substances

  • DNA