scholarly journals Identification of microsatellite markers <1 Mb from the FMR1 CGG repeat and development of a single-tube tetradecaplex PCR panel of highly polymorphic markers for preimplantation genetic diagnosis of fragile X syndrome

2016 ◽  
Vol 18 (9) ◽  
pp. 869-875 ◽  
Author(s):  
Min Chen ◽  
Mingjue Zhao ◽  
Caroline G. Lee ◽  
Samuel S. Chong
Keyword(s):  
Microsatellite Markers ◽  
Fragile X Syndrome ◽  
Preimplantation Genetic Diagnosis ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
Polymorphic Markers ◽  
Cgg Repeat ◽  
Single Tube

Preimplantation genetic diagnosis of the fragile X syndrome by use of linked polymorphic markers

2001 ◽  
Vol 21 (6) ◽  
pp. 504-511 ◽  
Author(s):  
A. Apessos ◽  
P. M. Abou-Sleiman ◽  
J. C. Harper ◽  
J. D. A. Delhanty
Keyword(s):  
Fragile X Syndrome ◽  
Preimplantation Genetic Diagnosis ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
Polymorphic Markers

scholarly journals Identification of Novel Microsatellite Markers <1 Mb from the HTT CAG Repeat and Development of a Single-Tube Tridecaplex PCR Panel of Highly Polymorphic Markers for Preimplantation Genetic Diagnosis of Huntington Disease

2016 ◽  
Vol 62 (8) ◽  
pp. 1096-1105 ◽  
Author(s):  
Mingjue Zhao ◽  
Min Chen ◽  
Caroline G Lee ◽  
Samuel S Chong
Keyword(s):  
Microsatellite Markers ◽  
Preimplantation Genetic Diagnosis ◽  
Huntington Disease ◽  
In Silico ◽  
Single Cells ◽  
Genetic Diagnosis ◽  
Cag Repeat ◽  
Polymorphic Markers ◽  
Single Tube ◽  
Direct Mutation

Abstract BACKGROUND Preimplantation genetic diagnosis (PGD) of Huntington disease (HD) generally employs linkage analysis of flanking microsatellite markers to complement direct mutation testing, as well as for exclusion testing. Thus far, only 10 linked markers have been developed for use in HD PGD, with a maximum of 3 markers coamplified successfully. We aimed to develop a single-tube multiplex PCR panel of highly polymorphic markers to simplify HD PGD. METHODS An in silico search was performed to identify all markers within 1 Mb flanking the huntingtin (HTT) gene. Selected markers were optimized in a single-tube PCR panel, and their polymorphism indices were determined in 2 populations. The panel was tested on 63 single cells to validate its utility in PGD. RESULTS We identified 102 markers in silico, of which 56 satisfied the selection criteria. After initial testing, 12 markers with potentially high heterozygosity were optimized into a single-tube PCR panel together with a 13th more distally located marker. Analysis of DNA from 183 Chinese and Caucasian individuals revealed high polymorphism indices for all markers (polymorphism information content &gt;0.5), with observed heterozygosities ranging from 0.5–0.92. All individuals were heterozygous for at least 5 markers, with 99.5% of individuals heterozygous for at least 2 markers upstream and downstream of the HTT CAG repeat. CONCLUSIONS The tridecaplex marker assay amplified reliably from single cells either directly or after whole genome amplification, thus validating its standalone use in HD exclusion PGD or as a complement to HTT CAG repeat expansion-mutation detection.

scholarly journals FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome

2017 ◽  
Vol 19 ◽  
Author(s):  
Indhu-Shree Rajan-Babu ◽  
Mulias Lian ◽  
Felicia S.H. Cheah ◽  
Min Chen ◽  
Arnold S.C. Tan ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Preimplantation Genetic Diagnosis ◽  
Haplotype Analysis ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
In Vitro Fertilisation ◽  
Marker Haplotype ◽  
Cgg Repeat ◽  
Robust Detection

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.

scholarly journals P23 Preimplantation genetic diagnosis for Fragile X syndrome

2010 ◽  
Vol 20 ◽  
pp. S30
Author(s):  
C. Fernandez ◽  
P. Blanchet ◽  
T. Anahory ◽  
L. Reyftman ◽  
S. Hamamah ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Preimplantation Genetic Diagnosis ◽  
Fragile X ◽  
Genetic Diagnosis

scholarly journals Fragile X syndrome carrier screening in pregnant women in Chinese Han population

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chia-Cheng Hung ◽  
Chien-Nan Lee ◽  
Yu-Chu Wang ◽  
Chih-Ling Chen ◽  
Tze-Kang Lin ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Fragile X Syndrome ◽  
Chinese Women ◽  
Fragile X ◽  
Genetic Diagnosis ◽  
Cost Effective ◽  
Carrier Screening ◽  
Chinese Han ◽  
Cgg Repeat ◽  
Taiwanese Women

Abstract Fragile X syndrome (FXS) is the most frequent genetic cause of intellectual disability (ID). It was previously believed that the FXS prevalence was low in Chinese population, and the cost-efficiency of FXS carrier screening was questioned. This retrospective observational study was conducted between September 2014 and May 2017 to determine the prevalence of FXS carriers in a large Chinese cohort of pregnant women. The FMR1 CGG repeat status was determined in 20,188 pregnant Taiwanese women and we identified 26 women with premutation (PM). The PM allele was transmitted to the fetus in 17 pregnancies (56.6%), and six of 17 expanded to full mutation (FM). One asymptomatic woman had a FM allele with 280 CGG repeats. Prenatal genetic diagnosis of her first fetus revealed a male carrying a FMR1 gene deletion of 5′ UTR and exon 1. Her second fetus was a female carrying a FM allele as well. This is so far the largest study of the FXS carrier screening in Chinese women. The prevalence of premutation allele for FXS in normal asymptomatic Taiwanese women was found to be as high as 0.13% (1 in 777) in this study. The empirical evidence suggests that reproductive FXS carrier screening in Taiwan might be cost-effective.

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