Next Article in Journal
Methylation Analysis of DNA Mismatch Repair Genes Using DNA Derived from the Peripheral Blood of Patients with Endometrial Cancer: Epimutation in Endometrial Carcinogenesis
Next Article in Special Issue
Associated Clinical Disorders Diagnosed by Medical Specialists in 188 FMR1 Premutation Carriers Found in the Last 25 Years in the Spanish Basque Country: A Retrospective Study
Previous Article in Journal
Congenital Cataracts and Gut Dysmotility in a DYNC1H1 Dyneinopathy Patient
Previous Article in Special Issue
Modeling Fragile X Syndrome Using Human Pluripotent Stem Cells
Article Menu

Export Article

Open AccessReview
Genes 2016, 7(10), 87; doi:10.3390/genes7100087

Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders

1
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore
2
Khoo Teck Puat—National University Children’s Medical Institute, National University Health System, Singapore 119228, Singapore
3
Department of Laboratory Medicine, National University Hospital, Singapore 119074, Singapore
*
Author to whom correspondence should be addressed.
Academic Editor: Mark Hirst
Received: 18 August 2016 / Revised: 6 October 2016 / Accepted: 8 October 2016 / Published: 14 October 2016
(This article belongs to the Special Issue Fragile X Syndrome)
View Full-Text   |   Download PDF [842 KB, uploaded 14 October 2016]   |  

Abstract

Fragile X syndrome (FXS) is the most common monogenic cause of intellectual disability and autism. Molecular diagnostic testing of FXS and related disorders (fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS)) relies on a combination of polymerase chain reaction (PCR) and Southern blot (SB) for the fragile X mental retardation 1 (FMR1) CGG-repeat expansion and methylation analyses. Recent advancements in PCR-based technologies have enabled the characterization of the complete spectrum of CGG-repeat mutation, with or without methylation assessment, and, as a result, have reduced our reliance on the labor- and time-intensive SB, which is the gold standard FXS diagnostic test. The newer and more robust triplet-primed PCR or TP-PCR assays allow the mapping of AGG interruptions and enable the predictive analysis of the risks of unstable CGG expansion during mother-to-child transmission. In this review, we have summarized the correlation between several molecular elements, including CGG-repeat size, methylation, mosaicism and skewed X-chromosome inactivation, and the extent of clinical involvement in patients with FMR1-related disorders, and reviewed key developments in PCR-based methodologies for the molecular diagnosis of FXS, FXTAS and FXPOI, and large-scale (CGG)n expansion screening in newborns, women of reproductive age and high-risk populations. View Full-Text
Keywords: fragile X syndrome; FXPOI; FXTAS; FMR1; AGG interruption; triplet-primed PCR; screening; CGG repeat; melting curve analysis; methylation fragile X syndrome; FXPOI; FXTAS; FMR1; AGG interruption; triplet-primed PCR; screening; CGG repeat; melting curve analysis; methylation
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Rajan-Babu, I.-S.; Chong, S.S. Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders. Genes 2016, 7, 87.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Genes EISSN 2073-4425 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top