New discovery links gene to incurable birth defect

Researchers from Melbourne-based medical research institute, WEHI, have discovered mutations in a gene can lead to an incurable neurodevelopmental disorder that causes abnormal brain development in newborns and infants.

The study published in Journal eLife reveals that a protein called Trabid helps control neuronal development, and that mutations to this protein can lead to microcephaly – a condition where a baby’s brain is smaller than expected.

Neurons are the fundamental building blocks of the nervous system, responsible for transmitting electrical and chemical signals that enable communication between different parts of the body and the brain.Microcephaly is a neurodevelopmental condition leading to an underdeveloped brain that adversely affects learning and behaviour

“Our understanding into how neurodevelopmental conditions, like microcephaly, develop continues to grow,” Assoc Prof Dewson, a Laboratory Head at WEHI, said. “While previous research has indicated there could be a link between defects in Trabid and microcephaly, our study is the first to provide evidence for the gene’s function in neuronal guidance –filling a vital knowledge gap.”

In 2015, UK researchers published a study that first suggested a possible connection between the gene encoding Trabid (ZRANB1) and microcephaly, after identifying two patients with the brain disorder who had mutations in this gene.

The researchers now suggest that the defects in Trabid, or the proteins that Trabid controls, could help identify babies who are at-risk of developing microcephaly – allowing for potential early interventions.

“Abnormalities in neuron migration and guidance can lead to neurodevelopmental disorders like microcephaly” said Dr HoanhTran.“Cells in the developing brain must migrate to the right location. If the address is missed, developmental defects can occur.Healthy neurons extend long processes called axons in a directional, ordered manner. In our study, we found the neurons from models with defective Trabid project axons that migrate with a wayward trajectory.These significant findings provide an understanding of Trabid/ZRANB1 as a new human microcephaly gene.”

References: DOI: 10.7554/eLife.90796.3