This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (89)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Genetic Counseling/ Testing/ Therapy  • Alert me on articles by topic

Yury Verlinsky, PhD; Svetlana Rechitsky, PhD; William Schoolcraft, MD; Charles Strom, MD,PhD; Anver Kuliev, MD,PhD

JAMA. 2001;285:3130-3133.

Context  The advent of single-cell polymerase chain reaction (PCR) has presented the opportunity for combined preimplantation genetic diagnosis (PGD) and HLA antigen testing. This is a novel and useful way to preselect a potential donor for an affected sibling requiring stem cell transplantation.

Objective  To perform in vitro fertilization (IVF) and preimplantation HLA matching combined with PGD for Fanconi anemia (FA).

Design  DNA analysis for the IVS 4 + 4 AT (adenine to thymine) mutation in the FA complement C (FANCC) gene in single blastomeres, obtained by biopsy of embryos, to identify genetic status and HLA markers of each embryo before intrauterine transfer.

Setting  In vitro fertilization programs at large medical centers in Chicago, Ill, and Denver, Colo.

Participants  A couple, both carriers of the IVS 4 + 4 AT mutation in the FANCC gene with an affected child requiring an HLA-compatible donor for cord blood transplantation.

Main Outcome Measures  DNA analysis of single blastomeres to preselect unaffected embryos representing an HLA match for the affected sibling.

Results  Of 30 embryos tested in 4 IVF attempts, 6 were homozygous affected and 24 were unaffected. Five of these embryos were also found to be HLA-compatible, of which 2 were transferred in the first and 1 in each of the other 3 cycles, resulting in a pregnancy and birth of an unaffected child in the last cycle.

Conclusion  To our knowledge, this is the first PGD with HLA matching, demonstrating feasibility of preselecting unaffected embryos that can also be an HLA-compatible source for stem cell transplantation for a sibling.

Author Affiliations: Reproductive Genetics Institute, Chicago, Ill (Drs Verlinsky, Rechitsky, Strom, and Kuliev); and Colorado Center for Reproductive Medicine, Denver (Dr Schoolcraft).

RELATED ARTICLES

Ethical Implications of a New Application of Preimplantation Diagnosis
Marian D. Damewood
JAMA. 2001;285(24):3143-3144.
EXTRACT | FULL TEXT  

June 27, 2001
JAMA. 2001;285(24):3197-3198.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

First Successful Bone Marrow Transplantation for X-linked Chronic Granulomatous Disease by Using Preimplantation Female Gender Typing and HLA Matching
Reichenbach et al.
Pediatrics 2008;122:e778-e782.
ABSTRACT | FULL TEXT  

Aneuploidy and early human embryo development
Ambartsumyan and Clark
Hum Mol Genet 2008;17:R10-R15.
ABSTRACT | FULL TEXT  

Laser-assisted derivation of human embryonic stem cell lines from IVF embryos after preimplantation genetic diagnosis
Turetsky et al.
Hum Reprod 2008;23:46-53.
ABSTRACT | FULL TEXT  

The Future (R)evolution of Preimplantation Genetic Diagnosis/Human Leukocyte Antigen Testing: Ethical Reflections
de Wert et al.
Stem Cells 2007;25:2167-2172.
ABSTRACT | FULL TEXT  

Cancer Genetic Testing and Assisted Reproduction
Offit et al.
JCO 2006;24:4775-4782.
ABSTRACT | FULL TEXT  

Stem Cell and Related Therapies: Nurses and midwives representing all parties
Cedar
Nurs Ethics 2006;13:292-303.
ABSTRACT  

Britain's new preimplantation tissue typing policy: an ethical defence
Ram
J. Med. Ethics 2006;32:278-282.
FULL TEXT  

Strategies and clinical outcome of 250 cycles of Preimplantation Genetic Diagnosis for single gene disorders
Fiorentino et al.
Hum Reprod 2006;21:670-684.
ABSTRACT | FULL TEXT  

Preimplantation HLA typing: having children to save our loved ones
Devolder
J. Med. Ethics 2005;31:582-586.
ABSTRACT | FULL TEXT  

Preimplantation Genetic Diagnosis--An Overview
Ogilvie et al.
J. Histochem. Cytochem. 2005;53:255-260.
ABSTRACT | FULL TEXT  

The role of preimplantation genetic diagnosis in the management of severe rhesus alloimmunization: first unaffected pregnancy: Case report
Seeho et al.
Hum Reprod 2005;20:697-701.
ABSTRACT | FULL TEXT  

Preimplantation Genetic Diagnosis (PGD) for Heritable Neoplasia
Simpson et al.
J Natl Cancer Inst Monogr 2005;2005:87-90.
ABSTRACT | FULL TEXT  

The Association of Radial Deficiency with Thumb Hypoplasia
James et al.
JBJS 2004;86:2196-2205.
ABSTRACT | FULL TEXT  

Isothermal whole genome amplification from single and small numbers of cells: a new era for preimplantation genetic diagnosis of inherited disease
Handyside et al.
Mol Hum Reprod 2004;10:767-772.
ABSTRACT | FULL TEXT  

Development and clinical application of a strategy for preimplantation genetic diagnosis of single gene disorders combined with HLA matching
Fiorentino et al.
Mol Hum Reprod 2004;10:445-460.
ABSTRACT | FULL TEXT  

Preimplantation HLA Testing
Verlinsky et al.
JAMA 2004;291:2079-2085.
ABSTRACT | FULL TEXT  

Hematopoietic Stem Cells
Trigg
Pediatrics 2004;113:1051-1057.
ABSTRACT | FULL TEXT  

Novel universal approach for preimplantation genetic diagnosis of {beta}-thalassaemia in combination with HLA matching of embryos
Van de Velde et al.
Hum Reprod 2004;19:700-708.
ABSTRACT | FULL TEXT  

Successful hematopoietic stem cell transplantation for Fanconi anemia from an unaffected HLA-genotype-identical sibling selected using preimplantation genetic diagnosis
Grewal et al.
Blood 2004;103:1147-1151.
ABSTRACT | FULL TEXT  

Extending preimplantation genetic diagnosis: medical and non-medical uses
Robertson
J. Med. Ethics 2003;29:213-216.
ABSTRACT | FULL TEXT  

Uses and abuses of genetic engineering
Alexander
Postgrad. Med. J. 2003;79:249-251.
FULL TEXT  

Extending preimplantation genetic diagnosis: the ethical debate: Ethical issues in new uses of preimplantation genetic diagnosis
Robertson
Hum Reprod 2003;18:465-471.
ABSTRACT | FULL TEXT  

Fanconi anaemia
Tischkowitz and Hodgson
J. Med. Genet. 2003;40:1-10.
ABSTRACT | FULL TEXT  

Preimplantation genetic diagnosis for {beta}-thalassaemia using sequencing of single cell PCR products to detect mutations and polymorphic loci
Hussey et al.
Mol Hum Reprod 2002;8:1136-1143.
ABSTRACT | FULL TEXT  

Preimplantation Diagnosis for Early-Onset Alzheimer Disease Caused by V717L Mutation
Verlinsky et al.
JAMA 2002;287:1018-1021.
ABSTRACT | FULL TEXT  

Molecular Diagnostics in Preimplantation Genetic Diagnosis
Thornhill and Snow
J. Mol. Diagn. 2002;4:11-29.
FULL TEXT  

Ethics of using preimplantation genetic diagnosis to select a stem cell donor for an existing person
Boyle and Savulescu
BMJ 2001;323:1240-1243.
FULL TEXT  

Preimplantation Genetic Diagnosis of Fanconi's Anemia
JWatch General 2001;2001:2-2.
FULL TEXT  

Ethical Implications of a New Application of Preimplantation Diagnosis
Damewood
JAMA 2001;285:3143-3144.
FULL TEXT