TY - JOUR
T1 - Noninvasive prenatal diagnosis of Huntington disease
T2 - Detection of the paternally inherited expanded CAG repeat in maternal plasma
AU - Van den Oever, Jessica M.E.
AU - Bijlsma, Emilia K.
AU - Feenstra, Ilse
AU - Muntjewerff, Nienke
AU - Mathijssen, Inge B.
AU - Bakker, Egbert
AU - Van Belzen, Martine J.
AU - Boon, Elles M.J.
N1 - Publisher Copyright: © 2015 John Wiley & Sons, Ltd.
PY - 2015/10
Y1 - 2015/10
N2 - Objective: With a shift towards noninvasive testing, we have explored and validated the use of noninvasive prenatal diagnosis (NIPD) for Huntington disease (HD). Methods: Fifteen couples have been included, assessing a total of n=20 pregnancies. Fetal paternally inherited CAG repeat length was determined in total cell-free DNA from maternal plasma using a direct approach by PCR and subsequent fragment analysis. Results: All fetal HD (n=7) and intermediate (n=3) CAG repeats could be detected in maternal plasma. Detection of repeats in the normal range (n=10) was successful in n=5 cases where the paternal repeat size could be distinguished from maternal repeat patterns after fragment analysis. In all other cases (n=5), the paternal peaks coincided with the maternal peak pattern. All NIPD results were concordant with results from routine diagnostics on fetal genomic DNA from chorionic villi. Conclusion: In this validation study, we demonstrated that all fetuses at risk for HD could be identified noninvasively in maternal plasma. Additionally, we have confirmed results from previously described case reports that NIPD for HD can be performed using a direct approach by PCR. For future diagnostics, parental CAG profiles can be used to predict the success rate for NIPD prior to testing.
AB - Objective: With a shift towards noninvasive testing, we have explored and validated the use of noninvasive prenatal diagnosis (NIPD) for Huntington disease (HD). Methods: Fifteen couples have been included, assessing a total of n=20 pregnancies. Fetal paternally inherited CAG repeat length was determined in total cell-free DNA from maternal plasma using a direct approach by PCR and subsequent fragment analysis. Results: All fetal HD (n=7) and intermediate (n=3) CAG repeats could be detected in maternal plasma. Detection of repeats in the normal range (n=10) was successful in n=5 cases where the paternal repeat size could be distinguished from maternal repeat patterns after fragment analysis. In all other cases (n=5), the paternal peaks coincided with the maternal peak pattern. All NIPD results were concordant with results from routine diagnostics on fetal genomic DNA from chorionic villi. Conclusion: In this validation study, we demonstrated that all fetuses at risk for HD could be identified noninvasively in maternal plasma. Additionally, we have confirmed results from previously described case reports that NIPD for HD can be performed using a direct approach by PCR. For future diagnostics, parental CAG profiles can be used to predict the success rate for NIPD prior to testing.
UR - http://www.scopus.com/inward/record.url?scp=84943348223&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/pd.4593
DO - https://doi.org/10.1002/pd.4593
M3 - Article
C2 - 25767004
SN - 0197-3851
VL - 35
SP - 945
EP - 949
JO - Prenatal diagnosis
JF - Prenatal diagnosis
IS - 10
ER -