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Mutated gene linked to both autism and intellectual disability.

Autism spectrum disorder and intellectual disability often occur together and may even share similar genetic causes. Researchers reporting in Cell Reports have now linked mutations in a particular gene to the two disorders in humans. By revealing these genetic changes and their potential impact on common brain processes, researchers may uncover treatment approaches that could benefit a variety of patients.

In a study of four families with a total of 16 individuals affected by a spectrum of cognitive and social impairments, the research team, led by investigators from Boston Children’s Hospital and Harvard Medical School, discovered two mutations in the CC2D1A gene that prevent the gene’s expression. When inherited from both parents, the lack of gene expression can cause mild to severe intellectual disability, autism, and/or seizures. The scientists then explored the function of this gene through experiments in mice.

A neuron must perform a very complex balancing act to respond to signals from other cells, and the researchers found that CC2D1A is a key component in controlling this balance.  A critical part of that balance involves the control of a signalling pathway that relies on NF-kappaB, a protein necessary for the survival and function of neurons. Reducing CC2D1A expression in mice led to decreased complexity of neurons and to increased NF-kappaB activity. Furthermore, the effects of CC2D1A depletion in neurons could be reversed by treating the mice with compounds that inhibit NF-kappaB activity.

The team hope that in the future, by fully understanding how this gene affects signalling in the brain, the medical community may be able to identify drugs to restore the normal signalling balance in neurons and improve cognitive and social function in patients.

In addition, by studying how the same exact genetic change can cause either intellectual disability or autism, researchers can explore how these disorders originate and where they overlap.

The researchers plan to investigate what percentage of individuals individuals with intellectual disability and autism may carry CC2D1A mutations and to determine whether other genes affect neurons in a similar fashion.

Source:  Harvard Medical School

 

(B) A simplified dendritic arbor was observed in cortical neurons at P11 following in utero electroporation of shRNA constructs at E15.5. Dendrites also appeared to be misoriented, terminating farther from the pial surface (red arrows). Scale bar, 50 μm.  (E) Hippocampal neurons at 7 and 14 DIV following Cc2d1a knockdown at 1 DIV also showed a reduction in total dendritic length caused by a reduction in process number. Average process length was not affected (n > 3 independent cultures).  Walsh et al 2014.
(B) A simplified dendritic arbor was observed in cortical neurons at P11 following in utero electroporation of shRNA constructs at E15.5. Dendrites also appeared to be misoriented, terminating farther from the pial surface (red arrows). Scale bar, 50 μm. (E) Hippocampal neurons at 7 and 14 DIV following Cc2d1a knockdown at 1 DIV also showed a reduction in total dendritic length caused by a reduction in process number. Average process length was not affected (n > 3 independent cultures). Walsh et al 2014.

Michelle Petersen View All

Michelle is a health industry veteran who taught and worked in the field before training as a science journalist.

Featured by numerous prestigious brands and publishers, she specializes in clinical trial innovation--expertise she gained while working in multiple positions within the private sector, the NHS, and Oxford University.

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