title: Preimplantation diagnosis for early-onset Alzheimer disease caused by V717L mutation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  An in vitro fertilization center in Chicago, Ill.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Reproductive Genetics Institute, Chicago, IL, USA. rgi@flash.net
authors.forename: Yury
authors.initials: Y
authors.lastname: Verlinsky
authors.forename: Svetlana
authors.initials: S
authors.lastname: Rechitsky
authors.forename: Oleg
authors.initials: O
authors.lastname: Verlinsky
authors.forename: Christina
authors.initials: C
authors.lastname: Masciangelo
authors.forename: Kevin
authors.initials: K
authors.lastname: Lederer
authors.forename: Anver
authors.initials: A
authors.lastname: Kuliev
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant; D005820:Genetic Testing; D006801:Humans; D007930:Leucine; D009154:Mutation; D010375:Pedigree; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis; D014633:Valine
chemical_list: D016564:Amyloid beta-Protein Precursor; D007930:Leucine; D014633:Valine