Double dose of genes linked to learning difficulties

Australian researchers have announced the identification of two genes that are involved in learning difficulties. Over 10,000 children born in the UK every year are affected by some form of developmental delay, but in 80 per cent of cases doctors are unable to determine a cause.

Reporting in the American Journal of Human Genetics, teams from the University of Adelaide, Katholieke Universiteit Leuven in Belgium and the Wellcome Trust Sanger Institute in Cambridge collaborated in scanning the X chromosome of 300 families using array CGH (comparative genomic hybridisation). This powerful new technique allows researchers to look for small gains and losses of DNA that may be at the root of learning difficulties.

The X chromosome, alongside Y, determines sex in humans. It is of particular interest to scientists studying learning difficulties, as 30 per cent of cases without a known cause are thought to originate from X chromosome disorders.

Women normally have two X chromosomes; while men have one X and one Y. X chromosome problems manifest in boys more than girls because in the event of a genetic mutation in one X chromosomes females have a 'back-up' copy. Males have no such redundancy. Women can potentially pass X-chromosome alterations on to their sons, leading to a physical or mental health problem, without showing any symptoms themselves.

The latest study revealed six families with a small segment of X chromosome DNA commonly duplicated. Two genes within the region caught researcher's eyes: HSD17B10 and HUWE1 have previously been shown to regulate brain cell growth.

The genes are causing particular excitement because the chromosomal duplication seen in the six families is increasing the production of protein from HSD17B10 and HUWE1. Although it has long been suspected, this is the first time proteins in excess have been proven to have a direct link to developmental problems.

There is the potential for rapid development of therapies from this breakthrough as it is easier to mop up excess protein than replace it - the customary goal of drug development. Dr Josef Gecz from Adelaide University said: 'Our next step is to see how frequent these mutations are among the isolated cases. Also, we will try to understand the molecular pathology of the associated disease and investigate the routes for possible future interventions and treatments'.