Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41598-019-52769-3
Title: Robust Preimplantation Genetic Testing of Huntington Disease by Combined Triplet-Primed PCR Analysis of the HTT CAG Repeat and Multi-Microsatellite Haplotyping
Authors: Zhao, M. 
Cheah, F.S.H.
Tan, A.S.C. 
Lian, M.
Phang, G.P.
Agarwal, A.
Chong, S.S. 
Issue Date: 2019
Publisher: Nature Publishing Group
Citation: Zhao, M., Cheah, F.S.H., Tan, A.S.C., Lian, M., Phang, G.P., Agarwal, A., Chong, S.S. (2019). Robust Preimplantation Genetic Testing of Huntington Disease by Combined Triplet-Primed PCR Analysis of the HTT CAG Repeat and Multi-Microsatellite Haplotyping. Scientific Reports 9 (1) : 16481. ScholarBank@NUS Repository. https://doi.org/10.1038/s41598-019-52769-3
Rights: Attribution 4.0 International
Abstract: Huntington disease (HD) is a lethal neurodegenerative disorder caused by expansion of a CAG repeat within the huntingtin (HTT) gene. Disease prevention can be facilitated by preimplantation genetic testing for this monogenic disorder (PGT-M). We developed a strategy for HD PGT-M, involving whole genome amplification (WGA) followed by combined triplet-primed PCR (TP-PCR) for HTT CAG repeat expansion detection and multi-microsatellite marker genotyping for disease haplotype phasing. The strategy was validated and tested pre-clinically in a simulated PGT-M case before clinical application in five cycles of a PGT-M case. The assay reliably and correctly diagnosed all embryos, even where allele dropout (ADO) occurred at the HTT CAG repeat locus or at one or more linked markers. Ten of the 27 embryos analyzed were diagnosed as unaffected. Four embryo transfers were performed, two of which involved fresh cycle double embryo transfers and two were frozen-thawed single embryo transfers. Pregnancies were achieved from each of the frozen-thawed single embryo transfers and confirmed to be unaffected by amniocentesis, culminating in live births at term. This strategy enhances diagnostic confidence for PGT-M of HD and can also be employed in situations where disease haplotype phase cannot be established prior to the start of PGT-M. © 2019, The Author(s).
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/209902
ISSN: 2045-2322
DOI: 10.1038/s41598-019-52769-3
Rights: Attribution 4.0 International
Appears in Collections:Elements
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1038_s41598-019-52769-3.pdf7.47 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

2
checked on Nov 24, 2022

Page view(s)

63
checked on Nov 17, 2022

Download(s)

1
checked on Nov 17, 2022

Google ScholarTM

Check

Altmetric


This item is licensed under a Creative Commons License Creative Commons