Tag Archives: SHANK3

Publications of the week – PRICKLE1, Phelan-McDermid syndrome, and mitochondrial genetics

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The week in review. It’s currently a bit quiet in the literature with respect to novel gene findings. However, there is plenty to explore about genes and variants we already know and their role in human epilepsy. This week’s selection of publications is about functional studies in a gene for progressive myoclonus epilepsy, the EEG signature in a microdeletion syndrome, and contribution of mitochondrial genetics in intractable epilepsy. Continue reading →

SHANK3, epilepsy, and the excitatory/inhibitory imbalance

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Postsynaptic. SHANK proteins are elements of the postsynaptic density, linking synaptic transmission with the cytoskeleton. Deletions in SHANK2 and SHANK3 are known genetic risk factors for a broad range of neurodevelopmental disorders. The role of the reciprocal duplications, however, has remained unclear. In recent paper in Nature, a novel mouse model expressing a SHANK3 transgene is investigated. The results of a mere 1.5 fold overexpression of the protein are dramatic, hinting at unanticipated mechanisms that regulate the balance between excitation and inhibition.  Continue reading →

Hypermutability of autism genes: lessons from genome sequencing

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Pushing past the exome. Family exome sequencing has become a standard technology to identify de novo mutations in neurodevelopmental disorders including autism, schizophrenia, intellectual disability and epilepsy. Despite the many advances in the field, exome data is confusing and difficult to interpret. Accordingly, we were wondering what the increase from exome sequencing to genome sequencing might add other than more data and more questions. Now, a recent paper in Cell reports on family-based whole-genome sequencing in autism. And some of the results are quite surprising. Continue reading →