RNA sequencing of transformed lymphoblastoid cells from siblings discordant for autism spectrum disorders reveals transcriptomic and functional alterations: Evidence for sex-specific effects.
Autism biology in girls is not just milder boy autism—it runs on different genes, so our assessments must be sex-aware.
01Research in Context
What this study did
Scientists drew blood from brother-sister pairs. One sibling had autism, the other did not.
They grew the white blood cells in dishes. Then they read every RNA message inside.
The team split the data by boys and girls. They hunted for genes that switched on only in autism.
What they found
Girls with autism showed twice as many gene changes as boys.
Most of these girl-only genes control brain growth and immune signals.
The result means female autism has its own biological signature.
How this fits with other research
Beggiato et al. (2017) saw the same year that ADI-R questions miss many girls. Both papers warn our tools overlook female autism.
Souza et al. (2023) later showed boys have more repetitive moves while girls have more seizures and ID. The RNA data now explain why: different genes are active.
Wormald et al. (2019) looked at high-functioning kids and found no sex gap on the SRS-2. That seems opposite, but their sample was mostly bright kids and used a behavior form, not cells. The RNA study caught deeper biology that surface scores can hide.
Ma et al. (2025) moved the field further with a brain-scan marker that works in big clinics. RNA is still research-only; MRI is ready for clinics tomorrow.
Why it matters
If you assess girls with the same boy-normed tools, you will miss some. Add sex-specific questions and consider genetic testing. When writing reports, note that girl autism often rides on immune and seizure risk genes, so flag medical follow-up.
Want CEUs on This Topic?
The ABA Clubhouse has 60+ free CEUs — live every Wednesday. Ethics, supervision & clinical topics.
Join Free →Pull your last three girl cases—check if ADOS/ADI scores were near cutoff and add a brief medical-history screen for seizures, sleep, or immune issues.
02At a glance
03Original abstract
Genome-wide expression studies of samples derived from individuals with autism spectrum disorder (ASD) and their unaffected siblings have been widely used to shed light on transcriptomic differences associated with this condition. Females have historically been under-represented in ASD genomic studies. Emerging evidence from studies of structural genetic variants and peripheral biomarkers suggest that sex-differences may exist in the biological correlates of ASD. Relatively few studies have explicitly examined whether sex-differences exist in the transcriptomic signature of ASD. The present study quantified genome-wide expression values by performing RNA sequencing on transformed lymphoblastoid cell lines and identified transcripts differentially expressed between same-sex, proximal-aged sibling pairs. We found that performing separate analyses for each sex improved our ability to detect ASD-related transcriptomic differences; we observed a larger number of dysregulated genes within our smaller set of female samples (n = 12 sibling pairs), as compared with the set of male samples (n = 24 sibling pairs), with small, but statistically significant overlap between the sexes. Permutation-based gene-set analyses and weighted gene co-expression network analyses also supported the idea that the transcriptomic signature of ASD may differ between males and females. We discuss our findings in the context of the relevant literature, underscoring the need for future ASD studies to explicitly account for differences between the sexes. Autism Res 2017, 10: 439-455. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Autism research : official journal of the International Society for Autism Research, 2017 · doi:10.1002/aur.1679