Preimplantation genetic diagnosis using fluorescent in situ hybridization for cancer predisposition syndromes caused by microdeletions

Hum Reprod. 2009 Jun;24(6):1522-8. doi: 10.1093/humrep/dep034. Epub 2009 Mar 10.


Background: Neurofibromatosis type 1 (NF1) and Von Hippel-Lindau (VHL) are dominantly inherited late onset cancer predisposition syndromes caused by mutations in the respective tumor suppressor genes (TSGs) NF1 and VHL. Less frequently TSGs are partially or fully deleted. Preimplantation genetic diagnosis (PGD) for cancer predisposition can be applied to select against the mutant allele in carrier couples. However, microdeletions within a single cell can, at present, not be detected by molecular diagnostic methods usually applied for PGD of monogenic disorders.

Methods: We performed PGD using interphase fluorescent in situ hybridization (FISH) on single blastomeres for three couples of which the women carried a microdeletion. One patient had the recurrent 1.4 Mb microdeletion covering NF1, a second suffered from an intragenic NF1 deletion and the last had a deletion of VHL.

Results: In total, seven PGD cycles were carried out for these couples, which resulted in the delivery of a healthy twin for the VHL microdeletion carrier.

Conclusions: FISH-based PGD is a straightforward approach to detect (micro)deletions in single blastomeres. It seems likely that the number of conditions for which PGD-FISH is beneficial will increase rapidly with the advent of high-resolution arrays.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Embryo Transfer
  • Female
  • Fertilization in Vitro
  • Gene Deletion
  • Humans
  • In Situ Hybridization, Fluorescence*
  • Neurofibromatosis 1 / diagnosis*
  • Neurofibromatosis 1 / genetics*
  • Ovulation Induction
  • Pregnancy
  • Pregnancy Outcome
  • Preimplantation Diagnosis*
  • von Hippel-Lindau Disease / diagnosis*
  • von Hippel-Lindau Disease / genetics*