Study links gene to inherited form of autism
Inherited mutations in a gene called ACTL6B lead to autism, epilepsy and intellectual disability, according to a new study1.
The mutations are recessive, which means that they lead to autism only if a person inherits them in both copies of the gene — one from each parent, who are silent carriers. Most other mutations implicated in autism are spontaneous, or ‘de novo,’ mutations, which are not inherited.
The study suggests that recessive mutations in ACTL6B could be a relatively common cause of autism, says co-lead researcher Joseph Gleeson, professor of neurosciences and pediatrics at the University of California, San Diego.
ACTL6B helps to control the expression of other genes in brain cells by encoding part of a protein complex called BAF. This complex tightens and loosens chromatin, the bundle of DNA and protein crammed inside a cell’s nucleus, during transcription. Scientists have linked autism to mutations in many other chromatin regulation genes — including several that encode other parts of the BAF complex.
ACTL6B mutations have previously been associated with neurodevelopmental conditions, but the new study makes a strong case that they are tied to autism, says Gaia Novarino, professor of neuroscience at the Institute of Science and Technology in Klosterneuburg, Austria, who was not involved in the study.
The work also provides a comprehensive look at how mutations in ACTL6B affect the brains of people, mice and flies, and suggests that the gene plays a common role across species.
The researchers searched a database of genetic sequences from autistic people, many with parents who are closely related — for example, first cousins. (Recessive mutations are common among the children of such parents.)
Recessive mutations in ACTL6B occur more frequently than expected among autistic people, they found, but not among 256 controls who have other developmental conditions. Among six families, they identified 13 autistic people who have two nonworking copies of ACTL6B.
All of the autistic individuals with ACTL6B mutations in both copies of the gene also have epilepsy and intellectual disability, conditions that would not have distinguished them from the rest of the members of the database.
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