title: Preimplantation genetic diagnosis (PGD) for a treatable disorder: Gaucher disease type 1 as a model.
abstract: BACKGROUND
  Preimplantation genetic diagnosis (PGD) is a technique that enables identification of unaffected embryos prior to in vitro fertilization (IVF) transfer in couples at risk for a Mendelian disorder. Most cases involve severe genetic diseases with neurological features and/or major malformations. We present two couples in which PGD was performed for prevention of type 1 Gaucher disease, a non-neuronopathic, non-lethal disorder.
  
  
  METHODS
  We developed a multiplex fluorescent PCR protocol, simultaneously amplifying the familial mutations and eight closely spaced, highly polymorphic informative microsatellite markers surrounding the gene, to be used for PGD analysis.
  
  
  RESULTS
  Couple #1 mother was homozygous for the N370S mutation and the father carried the 84GG mutation; their first daughter receives specific Gaucher therapy. One PGD cycle resulted in seven embryos of which four had the paternal wild type allele; two were transferred resulting in a healthy baby boy born at term. Couple #2, each a carrier (N370S and R359Q), whose first-born child had died (age 5years) of Gaucher disease, underwent 7 PGD cycles. Only one cycle resulted in a clinical pregnancy but a miscarriage was followed at 10weeks.
  
  
  CONCLUSIONS
  PGD is an effective and accurate method for preventing Gaucher disease type I in carrier couples. Since this disease is treatable, special ethical considerations and careful selection of couples should be performed.
authors.affiliation: Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. gheona@szmc.org.il
authors.forename: Gheona
authors.initials: G
authors.lastname: Altarescu
authors.forename: Paul
authors.initials: P
authors.lastname: Renbaum
authors.forename: Talia
authors.initials: T
authors.lastname: Eldar-Geva
authors.forename: Irit
authors.initials: I
authors.lastname: Varshower
authors.forename: Baruch
authors.initials: B
authors.lastname: Brooks
authors.forename: Rachel
authors.initials: R
authors.lastname: Beeri
authors.forename: Ehud J
authors.initials: EJ
authors.lastname: Margalioth
authors.forename: Ephrat
authors.initials: E
authors.lastname: Levy-Lahad
authors.forename: Deborah
authors.initials: D
authors.lastname: Elstein
authors.forename: Ari
authors.initials: A
authors.lastname: Zimran
mesh_terms: D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005776:Gaucher Disease / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D011247:Pregnancy; D019836:Preimplantation Diagnosis