Preimplantation diagnosis for Fanconi anemia combined with HLA matching

JAMA. 2001 Jun 27;285(24):3130-3. doi: 10.1001/jama.285.24.3130.


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 A-->T (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 A-->T 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.

MeSH terms

  • Blastomeres
  • DNA Mutational Analysis*
  • Fanconi Anemia / diagnosis*
  • Fanconi Anemia / genetics
  • Genetic Testing*
  • Histocompatibility Testing*
  • Humans
  • Polymerase Chain Reaction
  • Preimplantation Diagnosis*