Genetic links to learning difficulties

Men's intellectual development can be impaired by gene mutations on the X chromosome, according to an international study by 70 researchers. The report, published in Nature Genetics, found that nine genes are linked to abnormal brain development in boys.

Poor brain development causes learning disabilities in two to three per cent of the population, but the problem is more prevalent in males. This is because women have two X chromosomes, meaning that a mutation on one chromosome can be counteracted by a normally functioning copy on the other chromosome. Men have only one X chromosome, therefore a mutation is much more likely to have serious consequences.

In the biggest investigation of its kind, an international group of scientists studied 208 families affected by X-linked learning disabilities. They sequenced 720 of the 800 known genes on the X chromosome. They were then able to search these for major mutations that might explain why some boys in these families had learning disabilities. They found nine new genes that, when knocked out by rare mutations, lead to intellectual impairment. This finding adds to 70 other genes on the X chromosome that have already been linked to abnormal brain development in boys.

The discovery is a landmark for new DNA sequencing approaches, which identify novel genes with significant clinical implications. But, scientists must be cautious when using this technique because the team also discovered that about one to two per cent of the genes on the X chromosome can be knocked out completely without having any biological effects. The presence of a knocked-out gene in an individual affected by a particular disease does not necessarily mean that the inactive gene is causing the disease.

Professor Mike Stratton, of the Wellcome Trust Sanger Institute near Cambridge, who led the research said: 'It is remarkable that so many protein-coding genes can be lost without any apparent effect on an individual's normal existence - this is a surprising result and further research will be necessary in this area'.

The new research can help inform reproductive choice. Couples at risk of passing on mutations on to their children could have their embryos screened to select girls, who are not at such a high risk of developing X linked conditions.