Identification of mutations in the PI3K-AKT-mTOR signalling pathway in patients with macrocephaly and developmental delay and/or autism.
Kit San Yeung, Winnie Wan Yee Tso, Janice Jing Kun Ip and 8 others
PMID 29296277WHAT IT FOUND
Ten of 21 children with macrocephaly and developmental delay or autism had PI3K-AKT-mTOR pathway mutations.
Children with a mutation had lower developmental quotient scores, and two mutations were mosaic and found at higher levels in mouth or saliva samples.
Key findings
01Ten of 21 children with macrocephaly and developmental delay, intellectual disability, or autism had pathogenic or likely pathogenic mutations in genes involved in the PI3K-AKT-mTOR pathway, giving a diagnostic yield of 47.6%.
02Mean developmental quotient scores were 62.8 in mutation-positive patients and 76.1 in mutation-negative patients.
03Two PIK3CA mutations were somatic mosaic, and mutation load was higher in saliva or buccal mucosa than in blood.
STILL TO COME
How it was doneWhat they foundWhat it means for PTsWhat it means for SLPs
Read the rest of this summary
You get three full summaries a month, free, and we do not ask for a card. Search, the TL;DRs and your library stay unlimited either way.
What it does not show
Only 21 children were studied, and the authors say the findings need confirmation in larger studies. Long-term follow-up was not available for all patients. The sequencing strategy was not uniform; kits and sample types changed during the study. Four patients had estimated developmental quotient scores rather than formal assessment scores. Patients were recruited after negative chromosomal microarray results and with macrocephaly, so the findings may not apply to all children with developmental delay or autism. The authors state that knowledge of this disease spectrum is limited.
Declared interests
The study was funded by the SK Yee Medical Research Fund, The Society for the Relief of Disabled Children, and HKU Seed Funding for Basic Research. The supplied text does not report author conflicts of interest.
The easy way to misread this
Do not read the 47.6% mutation rate as proof that genetic testing will change therapy or that every child with macrocephaly and developmental delay has a PI3K-AKT-mTOR mutation. The study included 21 children selected after negative chromosomal microarray results, and the authors say the findings need confirmation in larger studies.