Early prenatal diagnosis of Hb Lepore Boston-Washington and β-thalassemia on fetal celomatic DNA

Int J Lab Hematol. 2022 Aug;44(4):796-802. doi: 10.1111/ijlh.13837. Epub 2022 Mar 25.

Abstract

Introduction: Analysis of fetal DNA in at risk couples for thalassemia is performed from fetal trophoblast or amniotic fluid cells. Although these procedures are in common use, the main limitation is essentially due to the late gestation week in which diagnosis is performed. The celomic cavity develops around 4 weeks of pregnancy within the extraembryonic mesoderm and contains embryonic erythroid precursor cells as a source of fetal DNA that can be used to perform invasive prenatal diagnosis.

Methods: Celomatic fluids were obtained at 8 weeks of gestation in thirteen women with high-risk pregnancies. Twelve of these couples were at risk for Hb Lepore disease and β-thalassemia and one couple represented a rare case in which both parents were carriers of Hb Lepore Boston-Washington. Fetal cells were isolated by micromanipulator and nested polymerase chain reactions were performed.

Results: The analysis was successfully performed in all examined cases. Two fetuses were found to have a compound heterozygosity for β-thalassemia and Hb Lepore Boston-Washington, three fetuses were found to be carriers of β-thalassemia, three fetuses of Hb Lepore, five were found without parental mutations. The genotypic analysis, carried out both by amniocentesis and on abortive tissue or after birth, showed concordance with results obtained on fetal celomic DNA.

Conclusion: Our results unequivocally show that fetal DNA can be obtained by nucleated fetal cells present in celomatic fluid and demonstrate for the first time that prenatal diagnosis of β-thalassemia and Hb Lepore may be feasible in an earlier time of pregnancy than other procedures.

Keywords: celocentesis; genetic test; monogenic disease; point mutation; thalassemia.

Publication types

  • Case Reports

MeSH terms

  • DNA / genetics
  • Female
  • Fetus / chemistry
  • Hemoglobins, Abnormal* / genetics
  • Humans
  • Pregnancy
  • Prenatal Diagnosis / methods
  • beta-Thalassemia* / diagnosis
  • beta-Thalassemia* / genetics

Substances

  • Hemoglobins, Abnormal
  • hemoglobin Lepore Boston-Washington
  • DNA