Seven more genes tied to brain disability affecting men

Defective genes on the X chromosome cause the disability, which is passed on in a recessive manner

Scientists have identified seven more genes that can cause X-linked intellectual disability, which predominantly affects men.

Defective genes on the X chromosome cause the disability. As men have only one X chromosome, the disability is passed on in a recessive manner. Women are affected only if both their X chromosomes carry the defective genes. Women with one healthy and one mutated X chromosome are usually free of the disability, but have a 50 per cent chance of passing the mutated chromosome on to their offspring.

Because of the highly variable symptoms of the disability, the search for its genetic cause was tedious until a few years ago. An international research team headed by Vera Kalscheuer from the Max Planck Institute for Molecular Genetics, Berlin, analysed 405 families with cases of the disability.

Discovery

“In addition to the known disease-related genes, we have discovered seven novel genes as the cause of X-linked intellectual disability and analysed what signalling pathways in the cells each protein is involved in,” Ms. Kalscheuer said.

Researchers said the symptoms and severity of the disorder depended on the responsible gene and the nature of the mutation. For example, if the mutation was located in a region important for brain development and protein function, the severity will be high.

With the help of systematic re-sequencing of all the X-linked genes, the genetic defect could be identified in around 60 per cent of the families with the disability.

For some years now, scientists have been aided in their research of genetic diseases by high-throughput sequencing, a technology which allows sequencing of many DNA segments simultaneously and helps identify genetic defects more easily. Using this method, the scientists investigated all DNA regions of the X chromosome containing protein-relevant information.