Cause of microcephaly discovered

Viennese researchers find gene mutation for severe developmental disorders of the brain

14/12/2012

A mutation of the gene Tubb5 should, according to a study of the Vienna Research Institute of Molecular Pathology (IMP) for the so-called microcephaly, a pathological reduction of the head, be responsible. About one in every ten thousand children is born with the severe developmental disorder that causes severe mental retardation.

Gene mutation disturbs stem cell pool and migration of nerve cells
The diminished brain growth can be caused by environmental stress such as alcohol abuse, but also by viral infection, such as rubella. A genetic defect is also a common trigger for microcephaly. The biologist David Keays from the IMP has now been able to identify together with the doctoral student Martin Breuss a gene that is said to be responsible for the malicious illness.

Tubb5 should therefore lead to impaired brain growth as a result of mutations. The researchers came to this conclusion, while in collaboration with scientists from Monash University in Australia, they specifically disrupted the brains of unborn mice with Tubb5. As a result, the mice developed impairment of the brain. In doing so, the stem cell reservoir was changed and the migration of nerve cells was impaired. Both the unrestricted supply of nerve cells from the stem cell pool as well as their positioning in the cerebral cortex are critical to brain development.

Tubb5 mutation allows conclusions about evolution
As the researchers in the latest issue of the online journal „Cell Reports ", the new findings are also interesting under the evolutionary aspect, because the number of neurons relative to body weight and their positioning in a strongly folded cerebrum are related to the development of monkeys to primates and on to humans.

Whether the new findings are also transferable to humans was examined by French physicians of the Paris Sorbonne. Among the patients with microcephaly, three children with a mutation of Tubb5 could be identified. „Our work is a good example of how insights from basic animal model research can be applied to human medicine“, explains Keays. For physicians, the discovery of this causal relationship is important to genetically advise parents with developmental children. It may also be possible to develop a targeted therapy in the long term. (Fp)

Also read about microcephaly:
Genetic defect of rare dwarfness decoded

Picture credits: Gerd Altmann