title: Singleton births after routine preimplantation genetic diagnosis using exclusion testing (D4S43 and D4S126) for Huntington's disease.
abstract: OBJECTIVE
  To develop exclusion testing protocols for Huntington's disease (HD) linkage markers suitable for use in a clinical preimplantation genetic diagnosis (PGD) setting for couples in whom a partner was at 50% risk of inheriting HD, but who choose not to undergo presymptomatic mutation testing.
  
  
  METHODS
  Preimplantation genetic diagnosis using exclusion testing.
  
  
  METHODS
  In vitro fertilization clinic.
  
  
  METHODS
  Three couples with family histories of HD, two couples opposed to direct mutation testing.
  
  
  METHODS
  Development of single-cell polymerase chain reaction tests for PGD for the HD mutation and two HD gene-flanking markers (D4S43 and D4S126), allowing the identification of an individual embryo as being at either low or high risk for developing HD without being diagnostic of the presence of the mutation.
  
  
  METHODS
  D4S43, D4S126, and HD mutation.
  
  
  RESULTS
  After PGD for HD, couple 1 gave birth to a healthy girl after a frozen embryo transfer, and genetic status was confirmed by prenatal diagnosis to be very low risk for developing HD. Couple 2 gave birth to a healthy boy after their second cycle of PGD, and couple 3, after a third cycle, gave birth to a boy with congenital heart defects, which were successfully corrected with surgery at age 5 days. Both couples 2 and 3 declined prenatal testing, and therefore relinquished the opportunity to confirm the PGD.
  
  
  CONCLUSIONS
  Preimplantation genetic diagnosis for HD using exclusion testing resulted in three live singleton births after six oocyte recovery procedures. The diagnostic protocol provided couples the opportunity to minimize the likelihood of disease transmission to their children, without the requirement for predictive testing.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Adelaide, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia. melinda.jasper@adelaide.edu.au
authors.forename: Melinda J
authors.initials: MJ
authors.lastname: Jasper
authors.forename: Dong Gui
authors.initials: DG
authors.lastname: Hu
authors.forename: Jan
authors.initials: J
authors.lastname: Liebelt
authors.forename: Deborah
authors.initials: D
authors.lastname: Sherrin
authors.forename: Robert
authors.initials: R
authors.lastname: Watson
authors.forename: Kelton P
authors.initials: KP
authors.lastname: Tremellen
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Hussey
mesh_terms: D000328:Adult; D015925:Cryopreservation; D004624:Embryo Transfer; D005260:Female; D005307:Fertilization in Vitro; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics; D007231:Infant, Newborn; D008297:Male; D036801:Parturition; D016133:Polymerase Chain Reaction; D019836:Preimplantation Diagnosis
chemical_list: D005819:Genetic Markers