Clinical impact and in vitro characterization of ADNP variants in pediatric patients.
Chuanhui Ge, Yuxin Tian, Chunchun Hu and 10 others
PMID 38254177WHAT IT FOUND
All 15 children with ADNP variants had global developmental delay.
Eight had autism, and 13 had distinctive facial features. In lab tests, most mutations disrupted how the protein sits in the cell nucleus, but not by blocking its entry signal alone.
Key findings
01All 15 children in the cohort exhibited global developmental delay or intellectual disability.
02Eight children received a clinical diagnosis of autism spectrum disorder, and 12 of 13 assessed showed autistic features.
03In vitro experiments showed that most ADNP variants disrupted the normal pattern of nuclear bodies, and some variants at the nuclear localization signal still allowed the protein to remain in the nucleus.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The study only included 15 children, which is a very small number for drawing general conclusions about the syndrome. The clinical data was cross-sectional, meaning it captured a single point in time rather than tracking how symptoms changed as the children grew. The lab results come from human cell lines, which may not behave exactly like neurons in a living human brain. There was significant variability in the severity of intellectual disability even among children with the exact same genetic mutation.
Declared interests
The study was funded by various Chinese government science foundations and grants, including the National Natural Science Foundation of China and the Shanghai Municipal Science and Technology Major Project. No commercial conflicts of interest were declared.
The easy way to misread this
Do not assume that a specific genetic mutation predicts the severity of a child's disability. The study found considerable variability in intellectual capacity even among children with identical ADNP variants, such as those with the p.R730* mutation who ranged from mild to severe impairment.