Singleton births after routine preimplantation genetic diagnosis using exclusion testing (D4S43 and D4S126) for Huntington's disease.
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.
Jasper
Melinda J
MJ
Department of Obstetrics and Gynaecology, University of Adelaide, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia. melinda.jasper@adelaide.edu.au
Hu
Dong Gui
DG
Liebelt
Jan
J
Sherrin
Deborah
D
Watson
Robert
R
Tremellen
Kelton P
KP
Hussey
Nicole D
ND
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
D005819:Genetic Markers