Pre-embryonic diagnosis for Sandhoff disease

Reprod Biomed Online. 2006 Mar;12(3):328-33. doi: 10.1016/s1472-6483(10)61005-x.


Embryos found to be abnormal during preimplantation genetic diagnosis (PGD) are discarded or analysed to confirm the diagnosis. To overcome this limitation, which is unacceptable in some communities and ethnic groups, pre-embryonic genetic diagnosis has been introduced, involving sequential first and second polar body analysis followed by transfer of embryos deriving from the mutation-free oocytes, while removing from culture and freezing the mutant oocytes at the pronuclear stage. The technique is applied here to PGD of Sandhoff disease caused by 16-kb deletion of the hexosaminidase B gene for a couple with a religious objection to discarding embryos irrespective of embryo genotype. Of 16 oocytes tested in a standard IVF protocol for 16-kb deletion, simultaneously with five linked polymorphic markers, eight were predicted mutant and frozen prior to syngamy, with the remaining eight, found to be free of mutation, further cultured and confirmed unaffected using blastomere biopsy. The transfer of two of these embryos resulted in birth of an unaffected child, demonstrating feasibility of pre-embryonic diagnosis to avoid embryo discard.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • DNA Mutational Analysis
  • Female
  • Hexosaminidase B
  • Humans
  • Male
  • Oocytes*
  • Pedigree
  • Pregnancy
  • Preimplantation Diagnosis / methods*
  • Sandhoff Disease / diagnosis*
  • Sandhoff Disease / genetics
  • Sequence Analysis, DNA
  • Sequence Deletion
  • beta-N-Acetylhexosaminidases / genetics


  • Hexosaminidase B
  • beta-N-Acetylhexosaminidases