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Tissue mosaicism, FMR1 expression and intellectual functioning in males with fragile X syndrome.
- Source :
- American Journal of Medical Genetics. Part A; Feb2023, Vol. 191 Issue 2, p357-369, 13p
- Publication Year :
- 2023
-
Abstract
- Fragile X syndrome (FXS) is caused by hypermethylation of the FMR1 promoter due to the full mutation expansion (full mutation [FM]: CGG ≥ 200 repeats) and silencing of FMR1. Assessment of mosaicism for active‐unmethylated alleles has prognostic utility. This study examined relationships between FMR1 methylation in different tissues with FMR1 messenger ribonucleic acid (mRNA) and intellectual functioning in 87 males with FXS (1.89–43.17 years of age). Methylation sensitive Southern blot (mSB) and Methylation Specific‐Quantitative Melt Aanalysis (MS‐QMA) were used to examine FMR1 methylation. FMR1 mRNA levels in blood showed strong relationships with FMR1 methylation assessed using MS‐QMA in blood (n = 68; R2 = 0.597; p = 1.4 × 10−10) and buccal epithelial cells (BEC) (n = 62; R2 = 0.24; p = 0.003), with these measures also showing relationships with intellectual functioning scores (p < 0.01). However, these relationships were not as strong for mSB, with ~40% of males with only FM alleles that were 100% methylated and non‐mosaic by mSB, showing methylation mosaicism by MS‐QMA. This was confirmed through presence of detectable levels of FMR1 mRNA in blood. In summary, FMR1 methylation levels in blood and BEC examined by MS‐QMA were significantly associated with FMR1 mRNA levels and intellectual functioning in males with FXS. These relationships were not as strong for mSB, which underestimated prevalence of mosaicism. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15524825
- Volume :
- 191
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- American Journal of Medical Genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 161228751
- Full Text :
- https://doi.org/10.1002/ajmg.a.63027