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Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
Author(s) -
De Franco E.,
Caswell R.,
Houghton J. A. L.,
Iotova V.,
Hattersley A. T.,
Ellard S.
Publication year - 2017
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.13180
Subject(s) - medicine , cell free fetal dna , diabetes mellitus , prenatal diagnosis , fetus , offspring , obstetrics , population , genetic testing , pregnancy , mutation , gestation , sanger sequencing , pediatrics , genetics , endocrinology , biology , gene , environmental health
Aims An early genetic diagnosis of neonatal diabetes guides clinical management and results in improved treatment in ~ 40% of patients. In the offspring of individuals with neonatal diabetes, a prenatal diagnosis allows accurate estimation of the risk of developing diabetes and, eventually, the most appropriate treatment for the baby. In this study, we performed non‐invasive prenatal genetic testing for a fetus at risk of inheriting a paternal KCNJ 11 p.R201C mutation causing permanent neonatal diabetes. Methods A droplet digital polymerase chain reaction assay was used to detect the presence of the mutation in cell‐free circulating DNA (cf DNA ) extracted from maternal plasma at 12 and 16 weeks’ gestation. Results The mutation was not detected in the cf DNA samples, suggesting that the fetus had not inherited the KCNJ 11 mutation. The fetal DNA fraction was estimated at 6.2% and 10.7%, which is above the detection limit of the assay. The result was confirmed by Sanger sequencing after the baby's birth, confirming that the baby's risk of developing neonatal diabetes was reduced to that of the general population. Conclusions We report the first case of non‐invasive prenatal testing in a family with neonatal diabetes. A prenatal diagnosis in families at high risk of monogenic diabetes informs both prenatal and postnatal management. Although the clinical impact of this novel technology still needs to be assessed, its implementation in clinical practice (including cases at risk of inheriting mutations from the mother) will likely have a positive impact upon the clinical management of families affected by monogenic diabetes.