Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly.
Marc Woodbury-Smith, Eric Deneault, Ryan K C Yuen and 11 others
PMID 29152164WHAT IT FOUND
Two brothers in one family with autism, intellectual disability, no functional language, fine motor problems, and head circumference on the 98th percentile shared a maternal RAB39B mutation.
Their sister had mild intellectual disability and autism traits, not autism; their mother had tremor.
Key findings
01Two brothers with autism spectrum disorder and intellectual disability had no functional language, fine motor difficulties, and macrocephaly.
02A nonsense variant in RAB39B exon 2 was identified in both males with autism spectrum disorder and inherited from their mother.
03The sister who carried the mutation had mild intellectual disability and a broad autism phenotype but not autism spectrum disorder, and the mother had a unilateral fine upper intention tremor of unknown etiology.
STILL TO COME
How it was doneWhat they foundWhat it means for OTsWhat it means for SLPs
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What it does not show
This is a case report of one family, so it cannot establish how common RAB39B mutations are or prove that the mutation caused the phenotype. The two brothers also had a CNTN6 loss-of-function mutation, and the authors state they cannot separate the contributions of RAB39B and CNTN6. The laboratory knockout used a different RAB39B mutation from the family's, so it shows possible gene-expression effects, not the exact family mutation's effect. The sister was not assessed for autism spectrum disorder in childhood; her autism-like traits were inferred from a maternally completed questionnaire at 29 years. The mother's tremor was of unknown cause, and the authors say it is unclear whether it is related to the RAB39B mutation. Extended family members were genotyped but not examined, and motor or neurodegenerative outcomes may change in later adulthood.
Declared interests
Funded by Genome Canada, Ontario Genomics Institute, Canada Foundation for Innovation, and Ontario Research Fund. No conflict-of-interest statement is supplied.
The easy way to misread this
Do not conclude that RAB39B mutations commonly cause autism or that this mutation alone explains the brothers' features. It was described in one family, both brothers also had a CNTN6 mutation, and the authors found only one further person with a RAB39B variant in 2620 autism genomes.