Preimplantation genetic diagnosis (PGD) for a treatable disorder: Gaucher disease type 1 as a model.
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.
Altarescu
Gheona
G
Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel. gheona@szmc.org.il
Renbaum
Paul
P
Eldar-Geva
Talia
T
Varshower
Irit
I
Brooks
Baruch
B
Beeri
Rachel
R
Margalioth
Ehud J
EJ
Levy-Lahad
Ephrat
E
Elstein
Deborah
D
Zimran
Ari
A
D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005776:Gaucher Disease / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D008297:Male; D011247:Pregnancy; D019836:Preimplantation Diagnosis