title: The impact of mosaicism in preimplantation genetic diagnosis (PGD): approaches to PGD for dominant disorders in couples without family history.
abstract: OBJECTIVE
  Mosaicism in certain dominant disorders may result in a 'non-Mendelian' transmission for the causative mutation. Preimplantation genetic diagnosis (PGD) is available for patients with inherited disorders to achieve an unaffected pregnancy. We present our experience for two female patients with different dominantly inherited autosomal disorders; neurofibromatosis type 1 (NF1) and tuberous sclerosis complex type 2 (TSC2).
  
  
  METHODS
  PGD protocol development was carried out using single cells from the patients. PGD was carried out on polar bodies and different embryonic cells.
  
  
  RESULTS
  Protocol development for NF1 using lymphocytes from the patient suggested mosaicism for the mutation. This was supported further by quantitative fluorescent-PCR performed on genomic DNA. During PGD, polar bodies and blastomeres lacked the mutation that probably was absent or present at very low levels in the patient's germline. Single lymphocyte analysis during protocol development for TSC2 did not indicate mosaicism; however, analysis of single buccal cells and multiple embryo biopsies across two consecutive IVF/PGD cycles confirmed gonosomal mosaicism.
  
  
  CONCLUSIONS
  The trend in PGD is for blastocyst biopsy followed by whole genome amplification, eliminating single cell analysis. In the case of certain dominantly inherited disorders, pre-PGD single cell analysis is beneficial to identify potential mosaicism that ensures robust protocols. © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Preimplantation Genetics Group, Institute for Women's Health, University College London, London, UK. r.naja@ucl.ac.uk.
authors.forename: Roy Pascal
authors.initials: RP
authors.lastname: Naja
authors.affiliation: Preimplantation Genetics Group, Institute for Women's Health, University College London, London, UK.
authors.forename: Seema
authors.initials: S
authors.lastname: Dhanjal
authors.affiliation: The Centre for Reproductive and Genetic Health, London, UK.
authors.forename: Alpesh
authors.initials: A
authors.lastname: Doshi
authors.affiliation: The Centre for Reproductive and Genetic Health, London, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Serhal
authors.affiliation: Preimplantation Genetics Group, Institute for Women's Health, University College London, London, UK.
authors.forename: Joy
authors.initials: J
authors.lastname: Delhanty
authors.affiliation: Preimplantation Genetics Group, Institute for Women's Health, University College London, London, UK.
authors.forename: Sioban B
authors.initials: SB
authors.lastname: SenGupta
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D009030:Mosaicism; D009456:Neurofibromatosis 1 / Q000175:diagnosis*; D011247:Pregnancy; D019836:Preimplantation Diagnosis; D014402:Tuberous Sclerosis / Q000175:diagnosis*