Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Hui Guo, Tianyun Wang, Huidan Wu and 42 others
PMID 30564305WHAT IT FOUND
Many autism risk genes were identified, multiple new mutations occurred in some patients, and inherited mutations had milder parent traits.
This supports a multifactorial model, not one-gene explanations, and gives no tested therapy change.
Key findings
01De novo mutations in 38 genes accounted for 4.83% of quality-controlled patients, and SCN2A was the most frequently mutated gene.
02Increasing number of de novo mutations was associated with affected status, and females showed a stronger association than males.
03Inherited CHD8 mutations were found in families, and parent carriers had nonverbal IQ scores below 80 and showed autistic traits.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
The number of patients with recurrent mutations was too few to make definitive genotype-phenotype correlations with specific genes. The multiple-hit associations were described as suggestive and need replication in larger cohorts. Clinical reevaluation of inherited mutations was possible for only three families with CHD8 mutations and one family with KMT5B mutations. The analysis was limited to exonic mutations in targeted genes, not whole-genome variants. No therapy intervention was tested, so the paper does not show how to change treatment. Participants came from clinical referring centers and prior autism exome datasets, not a general population sample.
Declared interests
Funding was from the National Natural Science Foundation of China, Simons Foundation, National Institutes of Health, and Howard Hughes Medical Institute. The supplied text does not list author conflicts or a statement that a sponsor designed the study.
The easy way to misread this
Do not read these genetic findings as evidence that any therapy works. The paper reports mutations and phenotype associations, not tested interventions, and several associations were not significant.