Prenatal Diagnosis of Congenital Factor XIII Deficiency Using Cell-Free Fetal DNA (cffDNA)

Abstract

Background: Congenital factor (F) XIII deficiency is a rare coagulation factor deficiency transmitted in an autosomal recessive manner. FXIII deficiency presents different clinical manifestations including intracranial hemorrhage (ICH), the most common cause of morbidity and mortality. Since ICH may occur in the neonatal period, prenatal diagnosis (PND) is an effective way to reduce neonatal ICH and related consequences. In this study, we investigated a noninvasive prenatal diagnosis (NIPD) method, cell-free fetal DNA (cffDNA) for PND in FXIII deficiency. Method: This study was conducted on 7 pregnant women in their first trimester. After extraction of cffDNA from maternal plasma, polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was performed to find the underlying F13A gene mutations previously identified in family members. PCR-RFLP also was carried out on post-natal DNA samples. Sanger sequencing was used to confirm the results.Results: PCR-RFLP results for cffDNA and post-natal DNA samples were identical, with Sanger sequencing confirming the results. Four cases were heterozygote for F13A gene mutations, while 3 were unaffected. Conclusion: cffDNA is a noninvasive and effective method for PND in congenital FXIII deficiency.