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Implementation of non-invasive, next-generation sequencing-based early prenatal diagnosis for Epidermolysis Bullosa (Uitto 3)

Project lead Prof Jouni Uitto
Organisation Thomas Jefferson University, Jefferson Medical College, Philadelphia, USA
Project budget USD 177,140.51
Start date / Duration 01. Dec 2018 / 24 months
Funder(s) / Co-Funder(s) DEBRA Austria, EB MSAP/EBEP Recommended
Research area EB genetics, epigenetics & biology

Project details

Short lay summary

Knowledge of the precise mutations in each family is important for accurate diagnosis and subclassification of EB, with the ability, in general terms, to predict the severity and the overall outcome of the disease. The mutations will also assist in genetic counselling, and forms the basis for prenatal testing, which currently can be done as early as 10th-week gestation. They can also aid in preimplantation genetic diagnosis before the pregnancy starts. Uitto's team is currently working on the implementation of non-invasive prenatal diagnosis for EB. If successful, this method would provide information on whether the fetus is affected or not by EB as early as the 5th-week gestation, which is just about at the time that a woman knows that she is pregnant. This prenatal determination would require a blood sample taken from the mother's arm. Such early knowledge of the outcome will lessen the anxiety associated with uncertainty whether the fetus is affected or not. Finally, recent studies have stressed the importance of identifying the specific mutations in each family, as a way to develop novel and precise treatments in the realm of personalised medicine.

Scientific summary

This application has been developed to refine capabilities for non-invasive prenatal diagnosis of EB at the early stages of pregnancy. We will analyse the fetal genome from free fetal DNA in maternal blood by advanced strategies of next-generation sequencing in families with a history of severe RDEB and mutations in COL7A1. Consecutive blood samples will be taken during the first trimester of pregnancy to allow determination of the earliest point at which non-invasive prenatal diagnosis can be successfully performed with precision. Verification of the prediction by NIPT is based on CVS at 10-weeks gestation or phenotypic and genotypic assessment at term.

Strategic relevance

Considering the impact of EB on the affected individuals, their parents and caregivers, prevention of recurrence of the disease in subsequent pregnancies can be a goal for many families. Prenatal diagnosis allows the opportunity to provide critical information to a pregnant woman who has previously had a child affected by EB. Chorionic villus samples (CVS) obtained as early as the 10th-week gestation or by amniocentesis from week 16 onwards involve invasive procedures with increased risk of fetal loss. To avoid such complications, this proposal aims at developing non-invasive tests through the analysis of free fetal DNA or identification and isolation of fetal cells from the maternal blood.

What did this project achieve?

Uitto and colleagues proved that this strategy is feasible: the team faced enormous challenges during the pandemic and only two families could be recruited. Moreover, in these cases, the information about the parental mutations was not yet available at the beginning of the study. Detection could only be done at a relatively late stage of pregnancy and not as early as as planned.


next-generation sequencing
Thomas Jefferson University
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