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Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes

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 mos...

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Autores principales: De Franco, E., Caswell, R., Houghton, J. A. L., Iotova, V., Hattersley, A. T., Ellard, S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096683/
https://www.ncbi.nlm.nih.gov/pubmed/27477181
http://dx.doi.org/10.1111/dme.13180
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author De Franco, E.
Caswell, R.
Houghton, J. A. L.
Iotova, V.
Hattersley, A. T.
Ellard, S.
author_facet De Franco, E.
Caswell, R.
Houghton, J. A. L.
Iotova, V.
Hattersley, A. T.
Ellard, S.
author_sort De Franco, E.
collection PubMed
description 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 KCNJ11 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 (cfDNA) extracted from maternal plasma at 12 and 16 weeks’ gestation. RESULTS: The mutation was not detected in the cfDNA samples, suggesting that the fetus had not inherited the KCNJ11 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.
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spelling pubmed-50966832017-04-01 Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes De Franco, E. Caswell, R. Houghton, J. A. L. Iotova, V. Hattersley, A. T. Ellard, S. Diabet Med Research 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 KCNJ11 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 (cfDNA) extracted from maternal plasma at 12 and 16 weeks’ gestation. RESULTS: The mutation was not detected in the cfDNA samples, suggesting that the fetus had not inherited the KCNJ11 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. John Wiley and Sons Inc. 2016-07-31 2017-04 /pmc/articles/PMC5096683/ /pubmed/27477181 http://dx.doi.org/10.1111/dme.13180 Text en © 2016 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
De Franco, E.
Caswell, R.
Houghton, J. A. L.
Iotova, V.
Hattersley, A. T.
Ellard, S.
Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
title Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
title_full Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
title_fullStr Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
title_full_unstemmed Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
title_short Analysis of cell‐free fetal DNA for non‐invasive prenatal diagnosis in a family with neonatal diabetes
title_sort analysis of cell‐free fetal dna for non‐invasive prenatal diagnosis in a family with neonatal diabetes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5096683/
https://www.ncbi.nlm.nih.gov/pubmed/27477181
http://dx.doi.org/10.1111/dme.13180
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