| Letter
to the Editor
OB/GYN May 2005
To the Editor:
In your March 2005 issue (Marik J. The case for preimplantation genetic diagnosis. The Female Patient. 2005;30[3]:10), I read Dr Marik's comments with interest. I am writing to you to provide a point of information regarding the limitations of preimplantation genetic diagnosis (PGD) that I believe will be important to your readers.
In the third column of the first page, Dr Marik states that if only one partner is a known cystic fibrosis (CF) carrier and the other is not known to be a carrier, PGD should still be done. As suggested by the previous paragraph, the noncarrier partner may have a false-negative CF screen and could be carrying the CF mutation variant yet to be characterized in the routine CF screening tests, and PGD of an embryo may diagnose the homozygous mutation affected embryo.
This is not quite the case. Preimplantation genetic diagnosis is not yet the "firewall" we hope it will some day be in preventing the passage of a deleterious gene to our progeny. With the exception of the rare spontaneous common mutation of a second CF allele, PGD will be no more successful in screening an embryo than it was in screening the assumed noncarrier partner. It will fail to identify an affected embryo as it failed to detect the assumed noncarrier parent. Therefore, in considering polymerase chain reaction (PCR) for single gene defects, PGD is most effective if both parents are first tested in advance of in vitro fertilization (IVF) therapy; the specific CF mutations, even if rare, are identified and a specific PCR probe created. (This is not always possible as Dr Marik nicely articulated in the never ending discovery of new mutations.) Then IVF therapy is done and embryos formed are tested for CF using these probes matched to the parental mutations. In summary, PGD by PCR screening is no better for the embryos than it is for the parents.
I have cared for couples where both partners are screened for CF and only one is identified as a carrier; the other, with hindsight, had a false negative CF screen. They presented with the unfortunate history of already having a child affected with CF. By then, testing the affected child for rare mutations of the gene and identifying the gene in the child was performed, and the gene mutation was confirmed to be present in the presumed noncarrier parent. Once we are aware of both mutation variants from each parent, PCR probes specific for these mutations are prepared and used with very effective embryo screening for this couple with their upcoming IVF therapy.
Thank you for your consideration of presenting this information in an upcoming issue of your journal.
Michael S. Mersol-Barg, MD
Birmingham, Mich
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