Please use this identifier to cite or link to this item: https://doi.org/10.1017/erm.2017.10
Title: FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome
Authors: Rajan-Babu, Indhu-Shree
Lian, Mulias
Cheah, Felicia SH
Chen, Min
Tan, Arnold SC
Prasath, Ethiraj B
Loh, Seong Feei 
Chong, Samuel S 
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Medicine, Research & Experimental
Research & Experimental Medicine
MULTIPLE DISPLACEMENT AMPLIFICATION
FULL-MUTATION
PRIMED PCR
PRACTICE GUIDELINES
MYOTONIC-DYSTROPHY
EXPANDED ALLELES
PREMUTATION
DNA
CARRIERS
DISEASE
Issue Date: 19-Jul-2017
Publisher: CAMBRIDGE UNIV PRESS
Citation: Rajan-Babu, Indhu-Shree, Lian, Mulias, Cheah, Felicia SH, Chen, Min, Tan, Arnold SC, Prasath, Ethiraj B, Loh, Seong Feei, Chong, Samuel S (2017-07-19). FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome. EXPERT REVIEWS IN MOLECULAR MEDICINE 19. ScholarBank@NUS Repository. https://doi.org/10.1017/erm.2017.10
Abstract: Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed polymerase chain reaction (TP-PCR) for robust detection of expanded FMR1 alleles, in parallel with linked multi-marker haplotype analysis of 13 highly polymorphic microsatellite markers located within 1 Mb of the FMR1 CGG repeat, and the AMELX/Y dimorphism for gender identification. The assay was optimised and validated on single lymphoblasts isolated from fragile X reference cell lines, and applied to a simulated PGD case and a clinical in vitro fertilisation (IVF)-PGD case. In the simulated PGD case, definitive diagnosis of the expected results was achieved for all ‘embryos’. In the clinical IVF-PGD case, delivery of a healthy baby girl was achieved after transfer of an expansion-negative blastocyst. FMR1 TP-PCR reliably detects presence of expansion mutations and obviates reliance on informative normal alleles for determining expansion status in female embryos. Together with multi-marker haplotyping and gender determination, misdiagnosis and diagnostic ambiguity due to allele dropout is minimised, and couple-specific assay customisation can be avoided.
Source Title: EXPERT REVIEWS IN MOLECULAR MEDICINE
URI: https://scholarbank.nus.edu.sg/handle/10635/226868
ISSN: 14623994
DOI: 10.1017/erm.2017.10
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