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- Title
Molecular Correlates and Recent Advancements in the Diagnosis and Screening of FMR1-Related Disorders.
- Authors
Rajan-Babu, Indhu-Shree; Chong, Samuel S.
- 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.
- Subjects
GENE mapping; MOSAICISM; DNA methylation; DIAGNOSIS of fragile X syndrome; INTELLECTUAL disabilities; POLYMERASE chain reaction
- Publication
Genes, 2016, Vol 7, Issue 10, p87
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes7100087