1. ¹Service de Biologie de la Reproduction – SIHCUS-CMCO, CHU de Strasbourg, 19, rue Louis Pasteur, BP120, 67303 Schiltigheim Cedex, France
2. ²Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163 1, rue Laurent Fries, F-67400 Illkirch Cedex, CU de Strasbourg, France

Correspondence: Dr S Viville, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP163 1, rue Laurent Fries, F-67400 Illkirch Cedex, CU de Strasbourg, France. Tel: +33 3 88 65 33 22; Fax: +33 3 88 65 32 01; E-mail: viville@igbmc.u-strasbg.fr

Received 23 March 2004; Revised 18 June 2004; Accepted 25 June 2004; Published online 6 October 2004.

Abstract

Huntington's disease (HD) is a late-onset neurodegenerative disorder transmitted as an autosomal dominant trait. The causative mutation was characterised in 1993. For HD carriers willing to create a family, prenatal diagnosis (PND) or preimplantation genetic diagnosis (PGD) based on the mutation identification can be offered. For at-risk persons who do not want to undergo presymptomatic testing (PT), an exclusion test can be proposed. With such a test, only ftuses or embryos that inherit an allele from the unaffected grandparent are considered as unaffected. In cases of PND, if the ftus has one allele of the affected grandparent, termination of pregnancy is proposed. In cases of PGD, only not at-risk embryos are transferred. Since the beginning of our PGD activity, we have had 43 PGD referrals for HD, of which 24 were from patients who know their genetic status and 19 from patients who do not wish to perform PT. We have developed 12 multiplex fluorescent PCR protocols applied at the single-cell level for PGD, some of which target the CAG repeat while others use two different polymorphic microsatellites. We present here these different protocols and their clinical applications, as well as the characterisation and use of a new highly polymorphic intragenic marker. Between May 2001 and December 2003, 39 PGD cycles have been performed for 17 couples, 11 of whom had a known genetic status and six who did not wish to perform PT, resulting in four pregnancies.