Advantages of multiple markers and polar body analysis in preimplantation genetic diagnosis for Alagille disease

Prenat Diagn. 2007 Apr;27(4):317-21. doi: 10.1002/pd.1668.

Abstract

Objective: The development of a preimplantation genetic diagnosis (PGD) protocol for Alagille syndrome (AGS), a rare autosomal dominant disorder with hepatic, cardiac and ophthalmologic involvement.

Methods: We developed a polar body (PB)-based multiplex fluorescent PCR reaction for a female affected with AGS. The protocol included analysis of the Jagged 1 (JAG1) familial mutation and five closely linked highly polymorphic markers (D20S162, D20S901, D20S894, and D20S186).

Results: In two cycles of PGD 9 of ten embryos were accurately diagnosed by assessment of first and second PBs, one embryo required additional blastomere biopsy.

Conclusions: This protocol takes advantage of the larger window of opportunity for transfer and the increased accuracy of diagnosis afforded by the combination of PB biopsy and multiple marker analysis. Two cycles resulted in the transfer of two and three mutation-free embryos and a subsequent pregnancy as measured by the rising hCG levels.

MeSH terms

  • Alagille Syndrome / diagnosis*
  • Alagille Syndrome / genetics
  • Alleles
  • Calcium-Binding Proteins / genetics*
  • Clinical Protocols
  • Female
  • Genetic Markers
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Jagged-1 Protein
  • Membrane Proteins / genetics*
  • Oocytes / physiology
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Reproductive Techniques, Assisted
  • Sensitivity and Specificity
  • Serrate-Jagged Proteins

Substances

  • Calcium-Binding Proteins
  • Genetic Markers
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • Serrate-Jagged Proteins