PMID- 19949337
OWN - NLM
STAT- MEDLINE
DCOM- 20100325
LR  - 20100113
IS  - 1531-698X (Electronic)
IS  - 1040-8703 (Linking)
VI  - 22
IP  - 1
DP  - 2010 Feb
TI  - Preimplantation genetic diagnosis for haematologic conditions.
PG  - 28-34
LID - 10.1097/MOP.0b013e3283350d77 [doi]
AB  - PURPOSE OF REVIEW: This review will inform the clinician about the application, 
      success rates and limitations of preimplantation genetic diagnosis (PGD) for 
      haematologic disease to enable clinicians to offer couples with reproductive risk 
      a realistic view of possible treatments. The molecular techniques used to 
      diagnose disease mutations are described, including the newest technologies using 
      whole genome amplification (WGA) and preimplantation genetic haplotyping (PGH) of 
      embryos. The history and ethics involved in performing PGD together with human 
      leukocyte antigen (HLA) testing (PGD-H) to create matched siblings suitable for 
      haematopoietic stem cell transplant (HSCT) are discussed. RECENT FINDINGS: The 
      greatest diagnostic hurdle in PGD is the paucity of molecular material in the 
      single embryonic cell. WGA allows amplification of the entire genome, which 
      greatly simplifies mutation analysis and increases the possibilities of multiple 
      simultaneous genetic diagnoses. PGH can be applied to the amplified material, and 
      may enable the application of PGD to the less common haematological mutations, 
      and the diagnosis of nonaffected male progeny in cases of X-linked haematologic 
      diseases. SUMMARY: PGD to exclude embryos carrying serious haematologic disease 
      is a viable alternative to prenatal diagnosis for couples who wish to avoid 
      having affected children and for whom therapeutic termination of affected 
      pregnancies is unacceptable. PGD is not available for all haematologic mutations, 
      is expensive, time consuming and does not guarantee a pregnancy. PGD-H is more 
      diagnostically and ethically challenging, especially when there is the time 
      constraint of urgent provision of HLA-matched stem cells for a sick sibling. To 
      date there is only a handful of reported cases of successful HSCT from siblings 
      created by embryo selection. The evolving technology of PGH following WGA may 
      increase the diagnostic scope and availability of PGD in the future, but certain 
      limitations will remain.
FAU - El-Toukhy, Tarek
AU  - El-Toukhy T
AD  - Centre for Preimplantation Genetic Diagnosis, Guy's and St. Thomas' Hospital NHS 
      Foundation Trust, London, UK. tarek.el-toukhy@gstt.nhs.uk
FAU - Bickerstaff, Helen
AU  - Bickerstaff H
FAU - Meller, Simon
AU  - Meller S
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Opin Pediatr
JT  - Current opinion in pediatrics
JID - 9000850
SB  - IM
MH  - Female
MH  - Haplotypes
MH  - Hematologic Diseases/*diagnosis/*genetics
MH  - Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility Testing
MH  - Humans
MH  - Pregnancy
MH  - *Preimplantation Diagnosis
RF  - 50
EDAT- 2009/12/02 06:00
MHDA- 2010/03/26 06:00
CRDT- 2009/12/02 06:00
PHST- 2009/12/02 06:00 [entrez]
PHST- 2009/12/02 06:00 [pubmed]
PHST- 2010/03/26 06:00 [medline]
AID - 10.1097/MOP.0b013e3283350d77 [doi]
PST - ppublish
SO  - Curr Opin Pediatr. 2010 Feb;22(1):28-34. doi: 10.1097/MOP.0b013e3283350d77.