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European Journal of Human Genetics (2012) 20, 368375
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ARTICLE
Preimplantation genetic diagnosis (PGD) for Huntingtons disease: the experience of three European centres
Maartje C Van Rij1,5, Marjan De Rademaeker2,5, Cline Moutou3,5, Jos CFM Dreesen1, Martine De Rycke2, Inge Liebaers2, Joep PM Geraedts1, Christine EM De Die-Smulders*,1 and Stphane Viville3,4 on behalf of the BruMaStra PGD working group
This study provides an overview of 13 years of experience of preimplantation genetic diagnosis (PGD) for Huntingtons disease (HD) at three European PGD centres in Brussels, Maastricht and Strasbourg. Information on all 331 PGD intakes for HD, couples reproductive history, PGD approach, treatment cycles and outcomes between 1995 and 2008 were collected prospectively. Of 331 couples for intake, 68% requested direct testing and 32% exclusion testing (with a preponderance of French couples). At the time of PGD intake, 39% of women had experienced one or more pregnancies. A history of pregnancy termination after prenatal diagnosis was observed more frequently in the direct testing group (25%) than in the exclusion group (10%; P0.0027). PGD workup was based on two approaches: (1) direct testing of the CAG-triplet repeat and (2) linkage
analysis using intragenic or anking microsatellite markers of the HTT gene. In total, 257 couples had started workup and 174 couples (70% direct testing, 30% exclusion testing) completed at least one PGD cycle. In total, 389 cycles continued to oocyte retrieval (OR). The delivery rates per OR were 19.8%, and per embryo transfer 24.8%, resulting in 77 deliveries and the birth of 90 children. We conclude that PGD is a valuable and safe reproductive option for HD carriers and couples at risk of transmitting HD.
European Journal of Human Genetics (2012) 20, 368375; doi:http://dx.doi.org/10.1038/ejhg.2011.202
Web End =10.1038/ejhg.2011.202; published online 9 November 2011
Keywords: preimplantation genetic diagnosis (PGD); Huntingtons disease (HD); HTT gene; exclusion testing; delivery rates; prenatal diagnosis
INTRODUCTIONHuntingtons disease (HD; MIM: 143100) is a progressive neuro-degenerative disorder seriously affecting the quality of life of patients and their families. Clinical signs are progressive motor disability featuring chorea, as well as mental disturbances such as cognitive decline, changes in personality and depression.1 The mean age of onset is 35 to 44 years and the median survival time...