Prevalence and phenotypic impact of rare potentially damaging variants in autism spectrum disorder.
Behrang Mahjani, Silvia De Rubeis, Christina Gustavsson Mahjani and 13 others
PMID 34615535WHAT IT FOUND
Rare potentially damaging variants were found in 27% of Swedish autistic disorder cases with both genetic tests and associated with intellectual disability and epilepsy, not speech/language or motor disorders.
Key findings
01Among 674 probands with both whole-exome and genotyping data, 182 (27%) carried at least one potentially damaging variant when a broad gene list was used.
02In the main potentially damaging single nucleotide variant analysis, the reported odds ratio for intellectual disability was 2.60 and for epilepsy was 1.76.
03Speech/language disorders and motor function disorders did not show significant associations with potentially damaging variants in the main register-based analyses.
STILL TO COME
How it was doneWhat they foundWhat it means for SLPs
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What it does not show
Phenotypes came from medical registers, so milder comorbidities may be missed if the person did not seek specialist services. Not all variants were validated by a second method, and some potentially damaging calls could be artifacts. The study did not use ACMG guidelines and lacked de novo information, so some variants classified as potentially damaging may be uncertain. It focused on autistic disorder, not the broader autism spectrum, so findings may not apply to less profound presentations. Many birth-related variables had missing values, and head circumference and birth measures are interdependent. Potentially damaging variant definitions relied on gene lists and size thresholds, and a later conservative reanalysis changed some classifications.
Declared interests
Funding came from the Beatrice and Samuel A. Seaver Foundation and the National Institute of Mental Health.
The easy way to misread this
Do not read this as evidence that genetic testing should guide therapy. The study used register diagnoses and found no significant association with speech/language or motor function disorders.