Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome

WDR47 is a microtubule associated protein particularly enriched in neurons in humans and mice and is a novel regulator of mouse corpus callosum (CC) development. 

This study provides the first evidence of a causal relationship between bi-allelic variants in the WDR47 gene and a complex neurodevelopmental syndrome characterized by corpus callosum dysgenesis (CCD), microcephaly and other neuroanatomical phenotypes in both humans and mice.

Early onset neuronal degeneration is the key factor driving the corpus callosum agenesis upon complete Wdr47 loss.

The authors show that alterations in mitochondrial homeostasis, microtubule dynamics, and axonal transport collectively contribute to the poor survival of Wdr47-deficient callosal projection neurons.

The severity and breadth of neuroanatomical phenotypes correlate with the degree of functional loss due to the human variants.

The authors believe that WDR47 variants should be considered in unexplained cases of corpus callosum dysgenesis and microcephaly, intellectual disability and epilepsy.

https://www.embopress.org/doi/full/10.1038/s44321-024-00178-z

https://sciencemission.com/Bi-allelic-variants-in-WDR47-cause-a-complex-neurodevelopmental-syndrome