Gene identified for the severe childhood disease PLAAND
The best laid PLAAns of mice and men - when brain development goes awry: April 2017
Scientists at the MRC Human Genetics Unit at the University of Edinburgh have identified the gene causing PLAAND, a severe genetic disease, where affected children fail to thrive and die in early childhood.
Children affected by PLAAND cannot walk, feed or talk, and there is currently no treatment or cure.
The team used studies in mice to show that mutations in the gene PLAA cause this severe genetic disease.
Fresh insights using these mouse models demonstrates that accumulation of damaged proteins, which in normal brains should be targeted for degradation, disrupts brain development and nerve cell function.
Within healthy individuals, our cells have developed mechanisms to “flag-up” damaged proteins with a chemical ”barcode” (known as the ubiquitin code) which directs them along the correct path to be destroyed. In PLAAND patients, cells have lost the ability to read this code and damaged proteins accumulate, causing problems with brain development/formation and circuitry.
While PLAAND is extremely rare, it affects similar mechanisms to those underlying more common types of neurodegeneration, such as Alzheimer’s Disease and Parkinson’s Disease. Insights into how this chemical code regulates brain development and function may enable future follow-up studies to uncover new drugs to treat this rare disease.
The study, published in American Journal of Human Genetics, was led by a team of researchers at MRC Human Genetics Unit in the Institute for Genetics and Molecular Medicine at The University of Edinburgh in collaboration with groups from Cambridge, Birmingham, Dundee and Saudi Arabia. It was funded by the Medical Research Council.
Epub ahead of print: http://www.cell.com/ajhg/fulltext/S0002-9297(17)30113-1.