An international research team headed by Vera Kalscheuer, Max Planck Institute for Molecular Genetics in Berlin has analysed 405 families, in which cases of X-linked intellectual disability occur.
Defective genes on the X chromosome cause X-linked intellectual disability. The disease is passed on in a recessive manner in men, as they possess only one X chromosome.
Women are affected only if both their X chromosomes carry the defective genes. Women with one healthy and one mutated X chromosome have a 50 percent chance of passing the mutated X chromosome on to their offspring.
The search for the responsible genetic defect was very tedious due to the high variability of the clinical picture.
Researchers have discovered changes in a number of genes that were already related to the disorder and mutations in seven other genes that were not associated with the disorder.
High-throughput sequencing allows sequencing of a large number of DNA segments simultaneously and identifies genetic defects. Scientists investigated all DNA regions of the X chromosome containing protein-relevant information.
"In addition to 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," said Kalscheuer.
The clinical presentation and severity of the disorder depend on the responsible gene and the nature of the mutation. With the help of systematic re-sequencing of all X-linked genes, the responsible genetic defect can be identified in around 60 percent of families with X-linked intellectual disability.