Non-invasive prenatal diagnosis of β-thalassemia by detection of the cell-free fetal DNA in maternal circulation: a systematic review and meta-analysis

Abstract

The discovery of fetal DNA (f-DNA) opens the possibility of early non-invasive procedure for detection of paternally inherited mutation of beta-thalassemia. Since 2002, some studies have examined the sensitivity and specificity of this method for detection of paternally inherited mutation of thalassemia in pregnant women at risk of having affected babies. We conducted a systematic review of published articles that evaluated using this method for early detection of paternally inherited mutation in maternal plasma. A sensitive search of multiple databases was done in which nine studies met our inclusion criteria. The sensitivity and specificity was 99 and 99 %, respectively. The current study found that detection of paternally inherited mutation of thalassemia using analysis of cell-free fetal DNA is highly accurate. This method could replace conventional and invasive methods.

In Utero Gene Therapy (IUGT) Using GLOBE Lentiviral Vector Phenotypically Corrects the Heterozygous Humanised Mouse Model and Its Progress Can Be Monitored Using MRI Techniques

“…Fetal gene transfer to the haematopoietic compartment 91 may offer a third option to couples with a prenatal diagnosis of a fetal congenital blood disorder, especially in the beta haemoglobinopathies 92 . For human therapy, non-invasive prenatal diagnostic techniques are being developed using maternal blood to diagnose fetal thalassaemia from 8–10 weeks of gestation 93 . This would allow enough time to deliver gene therapy to the human fetus using ultrasound-guided intrahepatic injection.…”

β-Thalassemia

“…Analyses of fetal cells in maternal blood and of fetal DNA in maternal plasma for the presence of the father's mutation are currently being conducted. 36 Preimplantation genetic diagnosis may be available for families in which disease-causing mutations have been identified. 37…”

Non‐invasive prenatal testing for fetal inheritance of maternal β‐thalassaemia mutations using targeted sequencing and relative mutation dosage: a feasibility study

“…Most studies have focused on exclusion of inheritance of paternal mutations. A recent meta‐analysis by Zafari et al describing detection of paternal β ‐thalassaemia mutations noted an overall sensitivity of 99%. However, there have been few studies concerning detection of the maternal mutation.…”