Enhancing fetal outcomes in GCK-MODY pregnancies: a precision medicine approach via non-invasive prenatal GCK mutation detection.

Autor:	Schwitzgebel VM; Pediatric Endocrine and Diabetes Unit, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, Geneva, Switzerland.; Diabetes Center of the Faculty of Medicine, University of Geneva, Geneva, Switzerland., Blouin JL; Genetic Medicine, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Dehos B; Division of Endocrinology and Diabetes, Spital Grabs, Grabs, Switzerland., Köhler-Ballan B; Department of Infectious Disease, Geneva University Hospitals, Geneva, Switzerland., Puder JJ; Department Women-Mother-Child, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland., Rieubland C; Department of Medical Genetics, Central Institute of the Hospitals, Hospital of the Valais, Valais, Switzerland., Triantafyllidou M; Division of Endocrinology, Diabetes and Clinical Nutrition, Luzerner Kantonsspital, Lucerne, Switzerland., Zanchi A; Department of Medicine, Service of Endocrinology, Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland., Abramowicz M; Genetic Medicine, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland., Nouspikel T; Genetic Medicine, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.; Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Jazyk:	angličtina
Zdroj:	Frontiers in medicine [Front Med (Lausanne)] 2024 Apr 30; Vol. 11, pp. 1347290. Date of Electronic Publication: 2024 Apr 30 (Print Publication: 2024).
DOI:	10.3389/fmed.2024.1347290
Abstrakt:	Background: Mutations in the GCK gene cause Maturity Onset Diabetes of the Young (GCK-MODY) by impairing glucose-sensing in pancreatic beta cells. During pregnancy, managing this type of diabetes varies based on fetal genotype. Fetuses carrying a GCK mutation can derive benefit from moderate maternal hyperglycemia, stimulating insulin secretion in fetal islets, whereas this may cause macrosomia in wild-type fetuses. Modulating maternal glycemia can thus be viewed as a form of personalized prenatal therapy, highly beneficial but not justifying the risk of invasive testing. We therefore developed a monogenic non-invasive prenatal diagnostic (NIPD-M) test to reliably detect the transmission of a known maternal GCK mutation to the fetus. Methods: A small amount of fetal circulating cell-free DNA is present in maternal plasma but cannot be distinguished from maternal cell-free DNA. Determining transmission of a maternal mutation to the fetus thus implies sequencing adjacent polymorphisms to determine the balance of maternal haplotypes, the transmitted haplotype being over-represented in maternal plasma. Results: Here we present a series of such tests in which fetal genotype was successfully determined and show that it can be used to guide therapeutic decisions during pregnancy and improve the outcome for the offspring. We discuss several potential hurdles inherent to the technique, and strategies to overcome these. Conclusion: Our NIPD-M test allows reliable determination of the presence of a maternal GCK mutation in the fetus, thereby allowing personalized in utero therapy by modulating maternal glycemia, without incurring the risk of miscarriage inherent to invasive testing. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Schwitzgebel, Blouin, Dehos, Köhler-Ballan, Puder, Rieubland, Triantafyllidou, Zanchi, Abramowicz and Nouspikel.)
Databáze:	MEDLINE
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