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Preliminary Communication
February 27, 2002

Preimplantation Diagnosis for Early-Onset Alzheimer Disease Caused by V717L Mutation

Author Affiliations

Author Affiliations: Reproductive Genetics Institute (Drs Verlinsky, Rechitsky, and Kuliev, Mr Verlinsky, and Ms Masciangelo) and IVF Illinois (Dr Lederer), Chicago.

JAMA. 2002;287(8):1018-1021. doi:10.1001/jama.287.8.1018

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 blood.

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.