Table of Contents
Molecular Biology International
Volume 2012 (2012), Article ID 797342, 9 pages
http://dx.doi.org/10.1155/2012/797342
Research Article

Prevention of Lysosomal Storage Diseases and Derivation of Mutant Stem Cell Lines by Preimplantation Genetic Diagnosis

1“ZOHAR” PGD Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel
2School of Medicine, The Hebrew University, Jerusalem, Israel
3Stem Cell Laboratory, Medical Genetics Institute, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel
4IVF Unit, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel
5Gaucher Clinic, Shaare Zedek Medical Center, P.O. Box 3235, Jerusalem 91031, Israel

Received 13 June 2012; Accepted 27 November 2012

Academic Editor: Mouldy Sioud

Copyright © 2012 Gheona Altarescu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Preimplantation genetic diagnosis (PGD) allows birth of unaffected children for couples at risk for a genetic disorder. We present the strategy and outcome of PGD for four lysosomal storage disorders (LSD): Tay-Sachs disease (TSD), Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (HS), and subsequent development of stem cell lines. For each disease, we developed a family-specific fluorescent multiplex single-cell PCR protocol that included the familial mutation and informative markers surrounding the mutation. Embryo biopsy and PGD analysis were performed on either oocytes (polar bodies one and two) or on single blastomeres from a six-cell embryo. We treated twenty families carrying mutations in these lysosomal storage disorders, including 3 couples requiring simultaneous analysis for two disorders (TSD/GD, TSD/balanced Robertsonian translocation 45XYder(21;14), and HS/oculocutaneus albinism). These analyses led to an overall pregnancy rate/embryo transfer of 38% and the birth of 20 unaffected children from 17 families. We have found that PGD for lysosomal disorders is a safe and effective method to prevent birth of affected children. In addition, by using mutant embryos for the derivation of stem cell lines, we have successfully established GD and HS hESC lines for use as valuable models in LSD research.