Please use this identifier to cite or link to this item: https://doi.org/10.1017/erm.2017.10
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dc.titleFMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome
dc.contributor.authorRajan-Babu, Indhu-Shree
dc.contributor.authorLian, Mulias
dc.contributor.authorCheah, Felicia SH
dc.contributor.authorChen, Min
dc.contributor.authorTan, Arnold SC
dc.contributor.authorPrasath, Ethiraj B
dc.contributor.authorLoh, Seong Feei
dc.contributor.authorChong, Samuel S
dc.date.accessioned2022-06-09T06:48:48Z
dc.date.available2022-06-09T06:48:48Z
dc.date.issued2017-07-19
dc.identifier.citationRajan-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
dc.identifier.issn14623994
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/226868
dc.description.abstractFragile 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.
dc.language.isoen
dc.publisherCAMBRIDGE UNIV PRESS
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiochemistry & Molecular Biology
dc.subjectMedicine, Research & Experimental
dc.subjectResearch & Experimental Medicine
dc.subjectMULTIPLE DISPLACEMENT AMPLIFICATION
dc.subjectFULL-MUTATION
dc.subjectPRIMED PCR
dc.subjectPRACTICE GUIDELINES
dc.subjectMYOTONIC-DYSTROPHY
dc.subjectEXPANDED ALLELES
dc.subjectPREMUTATION
dc.subjectDNA
dc.subjectCARRIERS
dc.subjectDISEASE
dc.typeReview
dc.date.updated2022-06-07T06:54:35Z
dc.contributor.departmentPAEDIATRICS
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1017/erm.2017.10
dc.description.sourcetitleEXPERT REVIEWS IN MOLECULAR MEDICINE
dc.description.volume19
dc.published.statePublished
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