Naja, RP;
Dhanjal, S;
Doshi, A;
Serhal, P;
Delhanty, J;
SenGupta, SB;
(2016)
The impact of mosaicism in preimplantation genetic diagnosis (PGD): approaches to PGD for dominant disorders in couples without family history.
Prenatal Diagnosis
, 36
(9)
pp. 864-870.
10.1002/pd.4874.
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Abstract
OBJECTIVES: 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.
| Type: | Article |
|---|---|
| Title: | The impact of mosaicism in preimplantation genetic diagnosis (PGD): approaches to PGD for dominant disorders in couples without family history |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/pd.4874 |
| Publisher version: | http://doi.org/10.1002/pd.4874 |
| Language: | English |
| Additional information: | © 2016 John Wiley & Sons, Ltd. This is the peer reviewed version of the following article: Naja, RP; Dhanjal, S; Doshi, A; Serhal, P; Delhanty, J; SenGupta, SB; (2016) The impact of mosaicism in preimplantation genetic diagnosis (PGD): approaches to PGD for dominant disorders in couples without family history. Prenatal Diagnosis , 36 (9) pp. 864-870. 10.1002/pd.4874, which has been published in final form at http://doi.org/10.1002/pd.4874. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Reproductive Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1512478 |
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