Clinical Genetics

Clinical and Reproductive Genetics

PGDThis translational research line deals with reproductive genetics and preimplantation genetic diagnosis (PGD). It is addressing studies at the interface of genetics and reproduction, (early) embryonic and fetal development, the transmission of the genetic material and the effects of abnormalities in this genetic material on fertility and reproduction, as well as on evaluation of results and safety of PGD. Long-term data on growth, health, psychomotor and socio-emotional outcome of PGD children are collated. Profiles and motives for PGD, as well as moral dilemmas of reproductive choice, are also studied.

New techniques for optimalization of PGD such as whole genome amplification, array technology, haplotyping and karyomapping are developed within the program and subsequently introduced in the PGD clinic. Basic research comprises the role of BRCA1 and BRCA2 in oocyte and early embryo developmental competence. This research is connected to the KWF sponsored project on fertility and PGD in BRCA patients.

PGD is still a morally sensitive technology, leading to societal debate about its acceptability. In collaboration with the group of prof. de Wert, ethical aspects of PGD and other artificial reproductive techniques are adressed. Moreover, targeted versus broad Non Invasive Prenatal molecular Testing (NIPT) is technically explored within the programme. NIPT has gone through a tremendous development during the last years. In our research program we are concentrating on the development of a NIPT-method to detect fetal Y and fetal trisomy 21, 18 and 13 early in pregnancy via maternal blood. The safety and risks of these innovations as well as the genetic counseling aspects are also studied.


Masoud Zamani Esteki, Triin Viltrop, Olga Tšuiko, Airi Tiirats, Mariann Koel, Margit Nõukas, Olga Žilina, Katre Teearu, Heidi Marjonen, Hanna Kahila, Jeroen Meekels, Viveca Söderström-Anttila, Anne-Maria Suikkari, Aila Tiitinen, Reedik Mägi, Sulev Kõks, Nina Kaminen-Ahola, Ants Kurg, Thierry Voet, Joris Robert Vermeesch & Andres Salumets. In vitro fertilization does not increase the incidence of de novo copy number alterations in fetal and placental lineages, Nature Medicine, November 2019. See also the video

Drüsedau M, Dreesen JC, Derks-Smeets I, Coonen E, van Golde R, van Echten-Arends J, Kastrop PM, Blok MJ, Gómez-García E, Geraedts JP, Smeets HJ, de Die-Smulders CE, Paulussen AD. PGD for hereditary breast and ovarian cancer: the route to universal tests for BRCA1 and BRCA2 mutation carriers. Eur J Hum Genet. 2013 Dec;21(12):1361-8.

Mersy E, Smits LJ, van Winden LA, de Die-Smulders CE; South-East Netherlands NIPT Consortium, Paulussen AD, Macville MV, Coumans AB, Frints SG. Noninvasive detection of fetal trisomy 21: systematic review and report of quality and outcomes of diagnostic accuracy studies performed between 1997 and 2012. Hum Reprod Update. 2013 Jul-Aug;19(4):318-29.

de Die-Smulders CE, de Wert GM, Liebaers I, Tibben A, Evers-Kiebooms G. Reproductive options for prospective parents in families with Huntington's disease: clinical, psychological and ethical reflections. Hum Reprod Update. 2013, May-Jun;19(3):304-15.

Sallevelt SC, Dreesen JC, Drüsedau M, Spierts S, Coonen E, van Tienen FH, van Golde RJ, de Coo IF, Geraedts JP, de Die-Smulders CE, Smeets HJ. Preimplantation genetic diagnosis in mitochondrial DNA disorders: challenge and success. J Med Genet. 2013 Feb;50(2):125-32.

de Jong A, Dondorp WJ, Frints SG, de Die-Smulders CE, de Wert GM. Advances in prenatal screening: the ethical dimension. Nat Rev Genet. 2011 Aug 18;12(9):657-63.

de Jong A, Dondorp WJ, Macville MV, de Die-Smulders CE, van Lith JM, de Wert GM. Microarrays as a diagnostic tool in prenatal screening strategies: ethical reflection. Hum Genet. 2013 Sep 28.

Depienne C, Bugiani M, Dupuits C, Galanaud D, Touitou V, Postma N, van Berkel C, Polder E, Tollard E, Darios F, Brice A, de Die-Smulders CE, Vles JS, Vanderver A, Uziel G, Yalcinkaya C, Frints SG, Kalscheuer VM, Klooster J, Kamermans M, Abbink TE, Wolf NI, Sedel F, van der Knaap MS. Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurol. 2013 Jul;12(7):659-68.

van Rij MC, de Die-Smulders CE, Bijlsma EK, de Wert GM, Geraedts JP, Roos RA, Tibben A. Evaluation of exclusion prenatal and exclusion preimplantation genetic diagnosis for Huntington's disease in the Netherlands. Clin Genet. 2013, Feb;83(2):118-24.

van Rij M, de Koning Gans P, Aalfs C, Elting M, Ippel P, Maat-Kievit J, Vermeer S, Verschuuren-Bemelmans C, van Belzen M, Belfroid R, Losekoot M, Geraedts J, Roos R, Tibben A, de Die-Smulders C, Bijlsma E. Prenatal testing for Huntington's disease in the Netherlands from 1998 to 2008. Clin Genet. 2013 Jan 25.

Team leader

Prof. Christine de Die-Smulders, MD

Research group

A. Paulussen, PhD; M. Zamani Esteki, PhD; Y. Arens, MD, PhD; R. Blok, PhD; S. Stevens, PhD; M. Macville, PhD; E. Coonen, PhD; L. van Osch, PhD; J. Dreesen; C. van Uum; J. Meekels; A. Stell; S. Sallevelt, MD, PhD; M. Heijligers; J. Gietel-Habets


GROW (research programme Reproduction and Early Development)


Department of Reproductive Medicine MUMC+
Department of Obstetrics and Gynaecology
Department of Medical Oncology MUMC+
Department Health, Ethics and Society Maastricht University
Alliance PGD the Netherlands (with UMC Utrecht, UMC Groningen and AMC Amsterdam)
Alliance PGD Brussels-Maastricht-Strasbourg (BruMaStra)
Dutch NIPT-consortium