Context Indications for preimplantation genetic diagnosis (PGD) have recently
been expanded to include disorders with genetic predisposition to allow only
embryos free of predisposing genes to be preselected for transfer back to
patients, with no potential for pregnancy termination.
Objective To perform PGD for early-onset Alzheimer disease (AD), determined by
nearly completely penetrant autosomal dominant mutation in the amyloid precursor
protein (APP) gene.
Design Analysis undertaken in 1999-2000 of DNA for the V717L mutation (valine
to leucine substitution at codon 717) in the APP
gene in the first and second polar bodies, obtained by sequential sampling
of oocytes following in vitro fertilization, to preselect and transfer back
to the patient only the embryos that resulted from mutation-free oocytes.
Setting An in vitro fertilization center in Chicago, Ill.
Patients A 30-year-old AD-asymptomatic woman with a V717L mutation that was identified
by predictive testing of a family with a history of early-onset AD.
Main Outcome Measures Results of mutation analysis; pregnancy outcome.
Results Four of 15 embryos tested for maternal mutation in 2 PGD cycles, originating
from V717L mutation–free oocytes, were preselected for embryo transfer,
yielding a clinical pregnancy and birth of a healthy child free of predisposing
gene mutation according to chorionic villus sampling and testing of the neonate's
Conclusion This is the first known PGD procedure for inherited early-onset AD resulting
in a clinical pregnancy and birth of a child free of inherited predisposition
to early-onset AD.