neurodevelopmental disorders

Childhood neurodevelopmental disorders have now been shown to possess shared genetic roots. A study published in Nature Neuroscience has identified a new risk variant in the MAP1A gene for autism and ADHD.

Both of these disorders have unknown causes but are known to be heritable and polygenic. Links between neurodevelopmental disorders are other traits are being found at an increasing rate, such as being left-handed and schizophrenia

Exome sequences of 13,000 children were gathered from the Danish Neonatal Screening Biobank and the Psychiatric Central Research Register – 8,000 of which were diagnosed with Autism Spectrum Disorder (ASD) and/or Attention Deficit Hyperactivity Disorder (ADHD). Current European figures put ASD prevalence at 1%, and ADHD at ~4%.

The sequences were examined for the frequency of certain DNA variants or mutations. The most common variant found was a protein-truncating variant. These mutations are either nonsense or frameshift (that result in early STOP codons or an insertion/deletion that alters the DNA sequence after it), resulting in a shorter protein.

The researchers collated the data and found a surprising overlap in the frequency of DNA variants between those with ASD and ADHD that was not present in the 5,000 strong control group. After further investigation they discovered microtubule associated protein 1 (MAP1A) was significantly associated with ASD/ADHD.

MAP1A is highly expressed in the brain and is important for the organisation of microtubules. These structures form part of the cytoskeleton and are essential for cell division, and consequentially neuronal development. Given their role in the control of neuron migration, microtubule-associated genes provide a potential cause for neurodevelopmental disorders.

ASD is a neurodevelopmental disorder that has a range of symptoms, the most common traits are altered social interaction and communication. In children this may be noticeable as delayed speech, dislike of physical contact, or altered play with others.  ADHD is common in people with ASD with some overlap in symptoms. The main symptoms are inattentiveness and hyperactivity. It was thought to be a disorder only in childhood, but it is now recognised that it persists into adulthood.

An associated gene variant can point to the biological mechanism behind a neurodevelopmental disorder, providing an insight of what has changed compared to those unaffected. This study highlights the importance of cross-disorder analysis and how it could be a highly effective way of identifying causal variants leading to a better clinical understanding and more effective therapies.

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