Preimplantation diagnosis for early-onset Alzheimer disease caused by V717L mutation

JAMA. 2002 Feb 27;287(8):1018-21. 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics*
  • DNA Mutational Analysis
  • Female
  • Genes, Dominant
  • Genetic Testing
  • Humans
  • Leucine
  • Mutation*
  • Pedigree
  • Pregnancy
  • Pregnancy Outcome
  • Preimplantation Diagnosis*
  • Valine


  • Amyloid beta-Protein Precursor
  • Leucine
  • Valine