Incomplete silencing of full mutation alleles in males with fragile X syndrome is associated with autistic features.
Emma K Baker, Marta Arpone, Solange M Aliaga and 21 others
PMID 31073396WHAT IT FOUND
In males with fragile X full mutation only, detectable FMR1 mRNA in blood was linked to more severe autism features, especially social communication, in those under 19.
It was not linked to lower intellectual functioning in the same comparison.
Key findings
01In full mutation males under 19 years, those with incomplete FMR1 mRNA silencing had higher overall autism and social affect severity scores than those with complete silencing, and the difference remained after correction for multiple comparisons.
02The same incomplete silencing group did not differ significantly from the complete silencing group on corrected intellectual functioning scores.
03Across fragile X males, FMR1 mRNA levels were associated with corrected verbal and full-scale IQ, but not with autism features; the intellectual associations were mainly driven by premutation/full mutation mosaic males.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The study is cross-sectional, so it cannot show how FMR1 mRNA and symptoms change over time or prove that mRNA causes autism features. FMR1 mRNA was measured in blood, not brain, and the analysis used bulk mRNA levels, so it may miss cells with very high or very low expression. The study assumed blood FMR1 mRNA levels correspond to FMRP levels, but it did not measure FMRP. The premutation/full mutation mosaic male and female groups were small, so findings in those groups are less stable. Some differences in autism scores were significant before multiple testing adjustment but did not remain significant after adjustment. Autism features and social anxiety overlap, and the study did not measure social anxiety, so higher autism scores may partly reflect anxiety. Only female control data were used for reference ranges of FMR1 mRNA. Intellectual functioning was assessed with different tests by age and country, and some tests had known limitations for fragile X profiles.
Declared interests
The supplied text does not give a detailed conflict-of-interest declaration. The publication types list non-U.S. government research support.
The easy way to misread this
Do not read detectable FMR1 mRNA in blood as a cause of autism or as a clinical test. The study measured bulk mRNA in blood at a single time point, did not measure FMRP or brain expression, and did not test a treatment. It also did not measure social anxiety, which can overlap with autism features.