Developmental Delay in Microcephaly Holds Genetic Base

Mutation of a single gene protein, WDR62, can slow down cell division during normal development of the baby and this may lead to an abnormally small brain – microcephaly, as per a study in collaboration with Chinese scientists at the University of Geneva (UNIGE), in the Journal of Cell Biology. Primary microcephaly is a rare but serious genetic defect where there is an improper brain development in the baby that causes intellectual and milestones delay. It affects between 1 in 30,000 and 1 in 250,000 people, depending on the region of the world. Consanguineous unions might be a common causal factor for primary microcephaly.

Microcephaly and Genetic Cause

For any new being to develop, cell division remains an essential mechanism that is precisely regulated by cables called "microtubules". This structure allows the genetic material to be distributed equally in the chromosome of developing cells.

"These microtubules continually assemble and disassemble to reach their proper size at any moment. To regulate their size, the cell uses a protein, katanin (from the Japanese katana for sword) in charge of cutting microtubules to the right length", says Patrick Meraldi, professor in the Department of Cell Physiology and Metabolism at UNIGE Faculty of Medicine and coordinator of the Translational Research Centre in Onco-haematology (CRTOH), who led this work.

Earlier studies had discovered that the most frequently mutated gene in microcephaly, ASPM, along with WDR62 is involved in the location and function of katanin – the molecular sword responsible for cutting microtubules.

The study thereby reveals that slight dysregulation in the mechanics of cell division is sufficient to slow down the distribution of chromosomes during development. This delay ultimately causes too many cells to die that would then result in the abnormally small size of the brain of people with primary microcephaly.

"Katanin seems to be the central mechanism of this developmental disease. However, the outcome of our work is much broader: it allows us to understand how cancer cells modify the system to divide endlessly and proliferate in the body," says Patrick Meraldi.

Source-Medindia